View
10
Download
0
Category
Preview:
Citation preview
Supported by Eli Lilly and Company.
Eli Lilly and Company has not influenced the content of this publication
Developed in association with the
European Thoracic Oncology Platform
ESMO Congress 2021
16–21 September 2021
Letter from Prof Rolf Stahel
Dear Colleagues
It is my pleasure to present this ETOP slide set which has been designed to highlight and summarise key findings in thoracic
cancers from the major congresses in 2021. This slide set specifically focuses on the ESMO Congress 2021 and is available
in 4 languages – English, French, Chinese and Japanese.
The area of clinical research in oncology is a challenging and ever changing environment. Within this environment we all value
access to scientific data and research which helps to educate and inspire further advancements in our roles as scientists,
clinicians and educators. I hope you find this review of the latest developments in thoracic cancers of benefit to you in your
practice. If you would like to share your thoughts with us we would welcome your comments. Please send any correspondence
to etop@etop.eu-org.
I would like to thank our ETOP members Drs Enriqueta Felip, Solange Peters, Martin Reck and Egbert Smit for their roles as
Editors – for prioritising abstracts and reviewing slide content. The slide set you see before you would not be possible without
their commitment and hard work.
Finally, we are also very grateful to Lilly Oncology for their financial, administrative and logistical support in the realisation of
this complex yet rewarding activity.
Yours sincerely,
Rolf Stahel
President, ETOP Foundation Council
ETOP Medical Oncology Slide Deck Editors 2021
Focus: biomarkers (all stages)
Dr Enriqueta Felip
Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain
Focus: advanced NSCLC (not radically treatable stage III & stage IV)
Dr Solange Peters
Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland
Focus: other malignancies, SCLC, mesothelioma, rare tumors
Dr Martin Reck
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany
Focus: early and locally advanced NSCLC (stages I–III)
Dr Egbert Smit
Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
4
Contents
• Screening, biomarkers and prevention
• Early stage and locally advanced NSCLC – Stages I, II and III
• Advanced NSCLC – Not radically treatable stage III and stage IV
– First line
– Later lines
• Other malignancies
– SCLC, mesothelioma and thymic epithelial tumors
Screening, biomarkers and prevention
6
LBA68: Clinical value of pre-treatment T-Cell receptors (TCR) repertoire in non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy – Abed A, et al
• Study objective
– To evaluate whether pre-treatment T-cell receptor repertoire metricsa can predict response to pembrolizumab
in patients with NSCLC
• Methods
– DNA samples were prospectively collected from 50 patients prior to treatment and TCR sequencing was
performed
– TCR repertoire variables were correlated with ORR, PFS, OS and immune-related toxicity
Abed A, et al. Ann Oncol 2021;32(suppl):Abstr LBA68aAssessed using Omcomine™ TCR-beta assay
7
LBA68: Clinical value of pre-treatment T-Cell receptors (TCR) repertoire in non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy – Abed A, et al
• Key results
Abed A, et al. Ann Oncol 2021;32(suppl):Abstr LBA68
Numbers of
unique clones
TCR Shannon
diversity
TCR evenness
No. of unique clonesN
o. o
f u
niq
ue
clo
ne
s
NR R
p=0.038
10000
8000
6000
4000
2000
0
NR R
Shannon diversity
p=0.021
1.1
1.0
0.9
0.8
0.7Sh
an
no
n d
ive
rsity
ORR
TCR clonality
PFS
PF
S
100
75
50
25
0
10008006004002000
Time, days
HR 0.40(95%CI 0.14, 1.17);
p=0.031
No. of unique clones
n=11
n=18
100
75
50
25
0
10008006004002000
Time, days
HR 0.4495%CI 0.16, 1.21)
p=0.041
Shannon diversity
n=19
n=10
100
75
50
25
0
10008006004002000
Time, days
HR 0.3195%CI 0.11, 0.94);
p=0.033
Evenness
n=6
n=23
Clonality100
75
50
25
0
10008006004002000
Time, days
HR 3.1895%CI 1.06, 9.53);
p=0.033
n=6
n=23PF
S
Low
High
8
LBA68: Clinical value of pre-treatment T-Cell receptors (TCR) repertoire in non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy – Abed A, et al
• Key results (cont.)
Abed A, et al. Ann Oncol 2021;32(suppl):Abstr LBA68
TCR Shannon
diversity
TCR evenness
No. of unique
clones
TCR
convergence
TCR clonality
Shannon diversity
Pts
with
to
xic
ity, %
15
10
25
0
HighLow
RR 1.67 (0.84–3.16)
p=0.135
Evenness
Pts
with
to
xic
ity, %
15
10
25
0
HighLow
RR 2.30 (1.27–2.45)
p=0.017
Toxicity
Nil toxicity
Clonality
Pts
with
to
xic
ity, %
15
10
25
0
HighLow
RR 2.30 (1.27–3.90)
p=0.017
No. of unique clones
Pts
with
to
xic
ity, %
HighLow
RR 0.92 (0.48–1.67)
p=0.55610
8
6
4
2
0
Convergence
Pts
with
to
xic
ity, %
HighLow
RR 0.73 (0.36–1.41)
p=0.28210
8
6
4
2
0
9
LBA68: Clinical value of pre-treatment T-Cell receptors (TCR) repertoire in non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy – Abed A, et al
• Key results (cont.)
– TRVB6-4, 10-2 and 10-3 gene usage appears to be more frequent among non-responders
• Conclusions
– In patients with NSCLC receiving pembrolizumab, low TCR diversity at baseline was associated with
significant improvements in ORR and PFS, but not OS
– Low TCR evenness and increased clonality were significantly associated with increased immune-related
toxicity
Abed A, et al. Ann Oncol 2021;32(suppl):Abstr LBA68
Early stage and locally advanced NSCLC –Stages I, II and III
11
LBA9: IMpower010: sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC – Felip E, et al
• Study objective
– To evaluate the efficacy and safety of adjuvant atezolizumab in patients with advanced NSCLC in the
IMpower010 study
Felip E, et al. Ann Oncol 2021;32(suppl):Abstr LBA9
R
1:1
Stratification
• Sex
• Stage (IB vs. II vs. IIIA)
• Histology
• PD-L1 statusa
Key patient inclusion criteria
• Stage IB (≥4 cm)–IIIA NSCLC
• Completely resected
• ECOG PS 0−1
(n=1280)
Best supportive care
(n=495)
Atezolizumab 1200 mg q3w
(16 cycles)
(n=495)
Cisplatin +
pemetrexed, docetaxel,
gemcitabine or vinorelbine
(1–4 cycles)
aTC2/3 and any IC vs. TC0/1 and IC2/3 vs. TC0/1 and IC0/1
Primary endpoint
• DFS
Secondary endpoints
• OS, safety
12
LBA9: IMpower010: sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC – Felip E, et al
• Key results
Felip E, et al. Ann Oncol 2021;32(suppl):Abstr LBA9
DFS by PD-L1 status
All-randomised stage II-IIIA population
Subgroup (including EGFR/ALK+) n HR (95%Cl)
PD-L1 status by SP263
TC <1% 383 0.97 (0.72, 1.31)
TC ≥1% 476 0.66 (0.50, 0.88)
TC 1–49% 247 0.87 (0.60, 1.26)
TC ≥50% 229 0.43 (0.27, 0.68)
All patients 882 0.79 (0.64, 0.96)
Subgroup (excluding EGFR/ALK+) n HR (95%Cl)
PD-L1 status by SP263
TC <1% 312 0.92 (0.65, 1.30)
TC ≥1% 410 0.62 (0.45, 0.86)
TC 1–49% 201 0.82 (0.54, 1.25)
TC ≥50% 209 0.43 (0.26, 0.71)
All patients 743 0.74 (0.59, 0.93)
0.1 1.0 10.0
HRAtezolizumab better BSC better
0.1 1.0 10.0
HRAtezolizumab better BSC better
13
LBA9: IMpower010: sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC – Felip E, et al
• Key results (cont.)
Felip E, et al. Ann Oncol 2021;32(suppl):Abstr LBA9
80 PD-L1 TC ≥1% stage II–IIIA All randomized stage II–IIIA70
60
50
40
30
20
10
0Atezolizumab
(n=73)
BSC
(n=102)
Atezolizumab
(n=147)
BSC
(n=189)
Atezolizumab
(n=156)
BSC
(n=203)
Pa
tie
nts
, %
ITT stage IB–IIIA69.9
66.7 67.3 66.1 65.4 64.5
54.8
46.1 47.6 46.0 46.2 45.3
11.0
35.3
12.9
32.3
12.2
32.0
13.7
19.7
14.818.6
14.3
9.65.9
11.68.5
10.98.4
16.4
Any treatment Chemotherapy CIT Targeted TKI Targeted mAb
Post-relapse systemic non-protocol anticancer therapy
Other post-relapse
treatments, n (%)
PD-L1 TC ≥1% stage II–IIIA All randomized stage II–IIIA ITT stage IB–IIIA
Atezolizumab (n=73) BSC (n=102) Atezolizumab (n=147) BSC (n=189) Atezolizumab (n=156) BSC (n=203)
Radiotherapy 32 (43.8) 48 (47.1) 54 (36.7) 72 (38.1) 54 (34.6) 76 (37.4)
Surgery 12 (16.4) 11 (10.8) 23 (15.6) 26 (13.8) 23 (14.7) 32 (15.8)
14
LBA9: IMpower010: sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC – Felip E, et al
• Key results (cont.)
Felip E, et al. Ann Oncol 2021;32(suppl):Abstr LBA9
30
25
20
15
10
5
0
Media
n tim
e t
o r
ela
pse,
mo
Range, mo
16.8 17.3
24.0
18.2
12.213.5
8.6
13.512.1 12.5
8.6
13.512.0
10.4
5.3
12.010.6 10.4
8.2
12.0 12.010.6
8.2
12.0
LR
only
Distant
only
LR and
distant
CNS
only
LR
only
Distant
only
LR and
distant
CNS
only
LR
only
Distant
only
LR and
distant
CNS
only
Median (range) time to any relapse: 17.6 mo (0.7–42.3)
Median (range) time to any relapse: 10.9 mo (1.3–37.3)
Median (range) time to any relapse: 12.4 mo (0.7–42.3)
Median (range) time to any relapse: 11.1 mo (0.8–42.1)
Median (range) time to any relapse: 12.3 mo (0.7–42.3)
Median (range) time to any relapse: 12.0 mo (0.8–42.1)
Atezo:
BSC:
PD-L1 TC≥1% stage II–IIIA All randomized stage II–IIIA ITT stage IB–IIIA
n=35 n=42 n=28 n=40 n=9 n=17 n=8 n=12 n=58 n=72 n=62 n=77 n=25 n=34 n=14 n=23 n=59 n=75 n=67 n=82 n=27 n=38 n=14 n=25
Time from randomization to relapse
Atezolizumab BSC
15
LBA9: IMpower010: sites of relapse and subsequent therapy from a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC – Felip E, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC, atezolizumab showed similar patterns of relapse compared with best
supportive care, at a slower rate in PD-L1 TC≥1 patients
– In an exploratory analysis, patients with PD-L1 TC 1–49% showed DFS benefit
Felip E, et al. Ann Oncol 2021;32(suppl):Abstr LBA9
Site of relapse, n (%)
Atezolizumab
(n=156)
BSC
(n=203)
Locoregional only 59 (37.8) 75 (36.9)
Distant only 67 (42.9) 82 (40.4)
CNS 16 (10.3) 29 (14.3)
Bone/bone marrow 14 (9.0) 14 (6.9)
Contralateral lung 10 (6.4) 16 (7.9)
Liver 10 (6.4) 8 (3.9)
Lymph node 8 (5.1) 11 (5.4)
Ipsilateral lung 6 (3.8) 8 (3.9)
Subcutaneous tissue 1 (0.6) 2 (1.0)
Other 16 (10.3) 15 (7.4)
Site of relapse, n (%)
Atezolizumab
(n=156)
BSC
(n=203)
Locoregional and distant 27 (17.3) 38 (18.7)
Bone/bone marrow 11 (7.1) 8 (3.9)
Contralateral lung 7 (4.5) 10 (4.9)
Liver 6 (3.8) 4 (2.0)
Lymph node 5 (3.2) 9 (4.4)
Ipsilateral lung 5 (3.2) 1 (0.5)
CNS 3 (1.9) 6 (3.0)
Subcutaneous tissue 1 (0.6) 0
Other 6 (3.8) 13 (6.4)
16
1170O: An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: characterisation of PORT efficacy in Lung ART (IFCT-0503, UK NCRI, SAKK) – Le Pechoux C, et al
• Study objective
– To investigate the survival benefit of post-operative radiotherapy in patients with mediastinal lymph node-
positive NSCLC in the Lung ART study
Le Pechoux C, et al. Ann Oncol 2021;32(suppl):Abstr 1170O
Primary endpoint
• DFS
Secondary endpoints
• OS, patterns of relapse, local failure, second
cancers, safety
R
1:1
Stratification
• Centre
• Administration of CT (none vs. post-op CT vs. pre-op CT)
• Histology (SCC vs. other)
• Extent of mediastinal lymph node involvement (0 vs. 1 vs. 2+)
• Use of pre-treatment PET scan (yes vs. no)
Key patient inclusion criteria
• Completely resected stage
III NSCLC
• Confirmed N2 nodal
involvement
• Pre- and /or post-operative
chemotherapy
• PS 0–2
(n=501)
Control
(n=249)
Conformal PORT (54 Gy/5.5 weeks)
(n=252)
17
1170O: An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: characterisation of PORT efficacy in Lung ART (IFCT-0503, UK NCRI, SAKK) – Le Pechoux C, et al
• Key results
Le Pechoux C, et al. Ann Oncol 2021;32(suppl):Abstr 1170O
PORT arm Control arm
Pro
ba
bili
ty, %
100
80
60
40
20
0
DFS
Death
Survival time, months
10896847260483624120
DM
MR
Pro
ba
bili
ty, %
100
80
60
40
20
0
Survival time, months
60483624120 108968472
DFS
Death
DM
MR
Event, n (%) PORT (n=144) Control (n=152) Total (n=296) HR (95%CI)a
Mediastinal relapse (MR) 36 (25) 70 (46) 106 (36) 0.45 (0.30, 0.69)
All distant metastases (DM) 87 (60) 74 (49) 161 (54) 1.17 (0.86, 1.60)
Including brain metastases (BM) 34 (24) 27 (18) 61 (21) 1.33 (0.78, 2.26)
Death 21 (15) 8 (5) 29 (10) 2.63 (1.18, 5.84)
aFine-Gray sub-distribution hazard model
18
1170O: An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: characterisation of PORT efficacy in Lung ART (IFCT-0503, UK NCRI, SAKK) – Le Pechoux C, et al
• Key results (cont.)
• Conclusions
– In patients with completely resected NSCLC and mediastinal N2 involvement, use of post-operative
radiotherapy reduced the risk of mediastinal recurrence, but had no significant impact on survival rate
– Prognostic factors associated with different DFS included quality of resection, extent of mediastinal
involvement and lymph node ratio
Le Pechoux C, et al. Ann Oncol 2021;32(suppl):Abstr 1170O
Prognostic factors for DFS HR p-value
Treatment arm radiotherapy (vs. control) 0.89 0.33
Gender female (vs. male) 0.73 0.02
Histology squamous cell carcinoma (vs. other) 0.71 0.03
N2 involvement with N1 involvement (left or right) (vs. without) 1.50 <0.01
Number of mediastinal nodes stations involved (vs. 1) 0.01
None 0.99
≥2 1.46
Quality of resection (vs. R0) <0.001
R (uncertain) 1.29
R1 (extra-capsular extension) 1.31
R2a 1.95
bTwo patients should not have been included
19
1151MO: Pathological response is an independent factor of overall survival and disease-free survival after neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase 2 trial – Wislez M, et al
• Study objective
– To assess the feasibility of preoperative neoadjuvant durvalumab in patients with early stage, resectable
NSCLC in the IFCT-1601 IONESCO study
Wislez M, et al. Ann Oncol 2021;32(suppl):Abstr 1151MO
Primary endpoint
• Complete surgical resection (R0)
Secondary endpoints
• Mortality (90 days post-operative), OS,
DFS, RR, safety
Key patient inclusion criteria
• Stage IB (≥4 cm)–IIIA (no N2)
NSCLC
• Baselines tissue specimen
available
• ECOG PS 0–1
(n=50)
Durvalumab 750 mg
D1, 15, 29
(n=46)
Surgery 2–14 days
after last infusion
(n=43)
Follow-up at
4 weeks,
6 months, or
1 year after surgery
20
1151MO: Pathological response is an independent factor of overall survival and disease-free survival after neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase 2 trial – Wislez M, et al
• Key results
Wislez M, et al. Ann Oncol 2021;32(suppl):Abstr 1151MO
Residual viable tumour cellsa (RVT %) is associated with OS and DFS
Cox model for OS
Hazard ratio and 95%CI
Cox model for DFS
Hazard ratio and 95%CI
Male (vs. female)
Stage IIA (vs. IB)
Stage IIB (vs. IB)
RVT (for increasing value)
Squamous cell carcinoma
(vs. adenocarcinoma)
PS 1 (vs. 0)
Age (for increasing value)
Pneumonectomy (vs. lobectomy)
PD-L1 ≥1% (vs. <1%)
0.01 0.1 1 10 100
Favours longer OS
HR LCL UCL
0.73
1.24
0.81
1.64
2.30
0.76
1.11
1.50
0.67
0.17
0.13
0.09
1.03
0.55
0.09
0.99
0.29
0.12
3.08
11.94
7.24
2.60
9.62
6.23
1.24
7.77
3.69
LCL UCL
0.01 0.1 1 10 100
Favours longer DFS
HR
1.42
1.27
0.77
1.71
1.31
0.30
0.96
0.56
0.54
0.46
0.25
0.16
1.08
0.49
0.04
0.89
0.12
0.10
4.41
6.30
3.63
2.69
3.50
2.29
1.04
2.52
2.92
aAnalysed using Cox regression model including patient characteristics (age, gender, PS,
smoking status), histology, PD-L1 TPS, stage and surgical procedure. % RVT was used as a
continuous variable using each 10% increase as a unit
21
1151MO: Pathological response is an independent factor of overall survival and disease-free survival after neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase 2 trial – Wislez M, et al
• Key results (cont.)
Conclusions
– In patients with resectable NSCLC, residual viable tumour cells was found to be an independent prognostic
factor for OS and DFS outcomes
Wislez M, et al. Ann Oncol 2021;32(suppl):Abstr 1151MO
n
Complete resection (R0), n (%) 46 41 (89.1)
BOR, n (%)
CR 46 0
PR 46 4 (8.7)
SD 46 36 (78.3)
PD 46 6 (13)
RVT, median (range)a 43 36.1 (0–73.3)
Complete pathological response, n, % 43 3 (7)
n=46
Major pathological response, n (%) 8 (18.6)
12-mo DFS, % (95%CI) 78.3 (63.4, 87.7)
12-mo OS, % (95%CI) 89.1 (75.8, 95.3)
18-mo DFS, % (95%CI) 73.7 (58.4, 84.1)
18-mo OS, % (95%CI) 89.1 (75.8, 95.3)
aDegree of pathologic response was measured using % of residual viable tumour cells
(RVT) in the primary tumour and in any involved lymph nodes
22
1172MO: Durvalumab consolidation in patients with stage III non-resecable NSCLC with driver genomic alterations – Riudavets Melia M, et al
• Study objective
– To assess the effectiveness of durvalumab in patients with stage III, unresectable NSCLC harbouring
oncogenic driver alterations
• Methods
– A multicentre, retrospective study performed on data collected from 323 patients between April 2015 and
October 2020 from 25 centres across Europe and US
– Oncogenic driver alterations included:
• EGFR, BRAF and KRAS mutations
• ALK and ROS1 rearrangements
Riudavets Melia M, et al. Ann Oncol 2021;32(suppl):Abstr 1172MO
23
PFS by driver of genomic alteration (dGA) status
1172MO: Durvalumab consolidation in patients with stage III non-resecable NSCLC with driver genomic alterations – Riudavets Melia M, et al
Median follow-up: 18.5 mo (95%CI 16.9, 21.0)
mPFS: 17.5 mo (95%CI 13.2, 24.9)
mOS: 47.0 mo (95%CI 47.0, NR)
Riudavets Melia M, et al. Ann Oncol 2021;32(suppl):Abstr 1172MO
PF
S, %
100
80
60
40
20
0
252020151050
Time, months
16406191146202280
14811193243
Non-dGA: 18 mo (95%CI 13.4, 28.3)
dGA: 14.9 mo (95% CI 8.1, NR)
p=1.0
No. at risk
Non-dGA
dGA
• Key results
24
1172MO: Durvalumab consolidation in patients with stage III non-resecable NSCLC with driver genomic alterations – Riudavets Melia M, et al
• Key results (cont.)
Riudavets Melia M, et al. Ann Oncol 2021;32(suppl):Abstr 1172MO
PFS by individual dGA
PF
S, %
100
80
60
40
20
0
No. at risk Time, months
302520151050
1122258
0379162326
0001259
EGFRm
KRASm
Other
KRASm: NR (95%CI 11.3, NR)
EGFRm: 9.0 mo (95%CI 5.8, NR)
Other driver: 7.8 mo (95%CI 3.9, NR)
p=0.02
mPFS, mo
(95%CI)
18-mo OS rate, %
(95%CI)
Overall dGA 14.9 (8.1, NR) 93.4 (84.7, 100)
KRASm (n=26)
KRASm G12C (n=8)
NR (14.9, NR)
NR (11.3, NR)
89.7 (76.8, 100)
87.5 (67.3, 100)
EGFRm (n=8)
EGFRm del19/ex21 (n=6)
9.0 (5.8, NR)
8.1 (5.8, NR)
100 (NR, NR)
100 (NR, NR)
BRAFm (n=5)
BRAFm V600E (n=4)
3.9 (3.9, NR)
8.4 (3.9, NR)
100 (NR, NR)
100 (NR, NR)
ALKr (n=4) 7.8 (7.7, NR) 100 (NR, NR)
25
1172MO: Durvalumab consolidation in patients with stage III non-resecable NSCLC with driver genomic alterations – Riudavets Melia M, et al
• Conclusions
– In patients with unresectable stage III NSCLC, durvalumab consolidation treatment showed greater benefit in
PFS in the KRAS mutation subgroup compared with other genomic alternations
– Analysis on a larger cohort is mandatory and ongoing
Riudavets Melia M, et al. Ann Oncol 2021;32(suppl):Abstr 1172MO
Advanced NSCLCNot radically treatable stage III and stage IV
First line
27
LBA42: COAST: an open-label, randomised, phase 2 platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC – Martinez-Marti A, et al
• Study objective
– To evaluate the efficacy and safety of durvalumab in combination with either oleclumab or monalizumab in
patients with stage III NSCLC following concomitant chemotherapy in the COAST study
Martinez-Marti A, et al. Ann Oncol 2021;32(suppl):Abstr LBA42
Primary endpoint
• ORR (RECIST v1.1, investigator assessed)
Secondary endpoints
• DoR, DCR, PFS, OS, safety, pharmacokinetics
R
1:1:1
Stratification
• Histology (adenocarcinoma
vs. other)
Key patient inclusion criteria
• Unresectable, locally
advanced stage III NSCLC
• No PD after prior CRT
• ECOG PS 0–1
(n=189) Durvalumab 1500 mg q4w +
monalizumab 750 mg q2w
(n=62)
Durvalumab 1500 mg q4w
(n=67)
Durvalumab 1500 mg q4w +
oleclumab 3000 mga
(n=60)
aOleclumab q2w for cycle 1 or 2, then q4w starting cycle 3
28
LBA42: COAST: an open-label, randomised, phase 2 platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC – Martinez-Marti A, et al
• Key results
Martinez-Marti A, et al. Ann Oncol 2021;32(suppl):Abstr LBA42
Antitumor activity by investigator assessment
Durvalumab
(n=67)
Durvalumab + oleclumab
(n=60)
Durvalumab + monalizumab
(n=62)
Confirmed ORR, n (%) [95%CI] 12 (17.9) [9.6, 29.2] 18 (30.0) [18.8, 43.2] 22 (35.5) [23.7, 48.7]
Confirmed + unconfirmed ORR, n (%) (95%CI) 17 (25.4) [15.5, 37.5] 23 (38.3) [26.1, 51.8] 23 (37.1) [25.2, 50.3]
ORR odds ratio (95%CI) - 1.83 (0.80, 4.20) 1.77 (0.77, 4.11)
Objective responses by RECIST, n (%)
CR 2 (3.0) 1 (1.7) 3 (4.8)
PR 15 (22.4) 22 (36.7) 20 (32.3)
SD 27 (40.3) 25 (41.7) 27 (43.5)
PD 15 (22.4) 7 (11.7) 7 (11.3)
NE 8 (11.9) 5 (8.3) 4 (6.5)
16-week DCR rate, n (%) [95%CI] 39 (58.2) [45.5, 70.2] 49 (81.7) [69.9, 90.5] 48 (77.4) [65.0, 87.1]
mDoR, mo (95%CI) [range]NR (2.3, NA)
[0.0+ to 17.5+]
12.9 (6.7, NA)
[0.0+ to 16.9+]
NR (9.0, NA)
[1.9+ to 18.4+]
29
LBA42: COAST: an open-label, randomised, phase 2 platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC – Martinez-Marti A, et al
• Key results (cont.)
Martinez-Marti A, et al. Ann Oncol 2021;32(suppl):Abstr LBA42
PFS by investigator assessment
Durvalumab
Durvalumab +
oleclumab
Durvalumab +
monalizumab
Events/patients, n 38/67 22/60 21/62
mPFS, mo (95%CI) 6.3 (3.7, 11.2) NR (10.4, NE) 15.1 (13.6, NE)
HR (95%CI) – 0.44 (0.26, 0.75) 0.66 (0.49, 0.85)
PF
S p
rob
abili
ty
1.0
0.8
0.6
0.4
0.2
0
Time, months
20181614121086420
No. at risk
037913162032325067
0591322303740464960
1161125354144465562
D
D + O
D + M
72.7%
64.8%
39.2%
Durvalumab + oleclumab (n=60)
Durvalumab + monalizumab (n=62)
Durvalumab (n=67)
30
LBA42: COAST: an open-label, randomised, phase 2 platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC – Martinez-Marti A, et al
• Key results (cont.)
• Conclusions
– In patients with stage III NSCLC, combined immunomodulation therapy including durvalumab provided
additional ORR and PFS benefit over durvalumab monotherapy, with no new safety signals reported
Martinez-Marti A, et al. Ann Oncol 2021;32(suppl):Abstr LBA42
TEAEs occurring in >15% of patients in
any arm, n (%)
Durvalumab
(n=66)
Durvalumab + oleclumab
(n=59)
Durvalumab + monalizumab
(n=61)
All grades Grade 3/4 All grades Grade 3/4 All grades Grade 3/4
≥1 TEAE 65 (98.5) 23 (34.8) 57 (96.6) 21 (35.6) 61 (100) 16 (26.2)
Cough 12 (18.5) 0 18 (30.5) 1 (1.7) 27 (44.3) 0
Dyspnoea 17 (25.8) 2 (3.0) 15 (25.4) 1 (1.7) 14 (23.0) 1 (1.6)
Pruritus 7 (10.6) 0 10 (16.9) 0 15 (24.6) 0
Asthenia 10 (15.2) 0 10 (16.9) 0 14 (23.0) 0
Hypothyroidism 10 (15.2) 0 9 (15.3) 0 12 (19.7) 0
Diarrhoea 7 (10.6) 1 (1.5) 7 (11.9) 0 12 (19.7) 0
Pneumonitis 11 (16.7) 0 11 (18.6) 0 10 (16.4) 1 (1.6)
Arthralgia 11 (16.7) 0 9 (15.3) 0 10 (16.4) 0
Pyrexia 6 (9.1) 0 8 (13.6) 0 10 (16.4) 0
Rash 6 (9.1) 0 9 (15.3) 0 8 (13.1) 0
Constipation 10 (15.2) 0 4 (6.8) 0 2 (3.3) 0
31
LBA44: Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small-cell lung cancer harboring EGFR mutations; WJOG9717L study – Kenmotsu H, et al
• Study objective
– To evaluate the efficacy and safety of 1L osimertinib + bevacizumab in patients with advanced EGFR+, non-
squamous NSCLC
Kenmotsu H, et al. Ann Oncol 2021;32(suppl):Abstr LBA44
Primary endpoint
• PFS (BICR)
Secondary endpoints
• PFS by investigator, ORR, OS, safety
R
1:1
Stratification
• Sex
• Clinical stage (IIIB-IV vs. recurrence)
• EGFR mutation (Del19 deletion vs. L858R)
Key patient inclusion criteria
• Advanced/recurrent, non-
squamous, NSCLC
• EGFR mutation positive
• Treatment naïve
• No symptomatic CNS
metastasis
• ECOG PS 0–1
(n=122)
Osimertinib 80 mg/day
(n=61)
Osimertinib 80 mg/day +
bevacizumab 15 mg/kg q3w
(n=61)
32
LBA44: Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small-cell lung cancer harboring EGFR mutations; WJOG9717L study – Kenmotsu H, et al
• Key results
Kenmotsu H, et al. Ann Oncol 2021;32(suppl):Abstr LBA44
PFS by BICR
Osimertinib
(n=61)
Osimertinib + bevacizumab
(n=61)
No. of events 33 33
mPFS, mo (95%CI) 20.2 (11.79, NE) 22.1 (19.81, NE)
1-year PFS rate, % (95%CI) 63.7 (49.5, 74.9) 73.8 (60.4, 83.3)
2-year PFS rate, % (95%CI) 44.5 (31.0, 57.2) 49.8 (36.1, 62.1)
Median follow-up: 30.4 months
HR 0.862 (60%CI 0.700, 1.060), (95%CI 0.531,1.397)
p=0.213 (one-sided)
Pro
gre
ssio
n-f
ree s
urv
iva
l
by t
he
BIC
R, %
100
75
50
25
0
Time, months
4842363024181260No. at risk
(censored)0 (28)17 (12)23 (8)27 (8)34 (7)47 (5)61 (0)
0 (28)20 (10)27 (6)36 (6)40 (6)54 (3)61 (0)
Osi
Osi + bev
Osimertinib
(n=61)
Osimertinib +
bevacizumab
(n=61)
mPFS by investigator, mo (95%CI) 17.1 (11.66, 30.62) 24.3 (20.01, 32.36)
1-year PFS, % (95%CI) 60.6 (46.9, 71.8) 77.8 (64.9, 86.5)
2-year PFS, % (95%CI) 39.8 (27.3, 52.0) 51.3 (37.7, 63.3)
ORR, % (95%CI) 86 (77, 96) 82 (72, 92)
mOS, mo (95%CI) NE (33.8, NE) NE (33.3, NE)
1-year OS, % (95%CI) 98.3 (88.8, 99.8) 90.2 (74.9, 99.5)
2-year OS, % (95%CI) 76.4 (63.5, 85.3) 81.7 (69.5, 89.5)
33
LBA44: Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small-cell lung cancer harboring EGFR mutations; WJOG9717L study – Kenmotsu H, et al
• Key results (cont.)
• Conclusions
– In patients with non-squamous, EGFR+ NSCLC, 1L osimertinib + bevacizumab failed to provide a significant
improvements in efficacy compared with osimertinib alone
Kenmotsu H, et al. Ann Oncol 2021;32(suppl):Abstr LBA44
TEAEs, n (%)Osimertinib
(n=60)
Osimertinib +
bevacizumab
(n=61)
Grade 3–5 29 (48.3) 34 (55.7)
Led to discontinuation 16 (26.7) 34 (55.7)
Led to dose modification 25 (41.7) 39 (63.9)
Led to dose reduction 0 3 (4.9)
Led to death 0 0
SAEs 12 (20.0) 20 (32.8)
Led to discontinuation 3 (5.0) 7 (11.5)
Osimertinib Osimertinib +
bevacizumabHR (95%CI)
Ever-smoker, n 31 23
mPFS, mo (95%CI) 13.6 (7.8, 19.9) 32.4 (19.8, NE) 0.481 (0.227, 1.019)
Never-smoker, n 30 38
mPFS, mo (95%CI) 32.5 (13.8, NE) 20.3 (13.7, 32.3) 1.444 (0.736, 2.833)
Exon 19 del, n 36 35
mPFS, mo (95%CI) 20.3 (9.6, NE) NE (20.1, NE) 0.622 (0.312, 1.240)
Exon 21 L858R, n 25 26
mPFS, mo (95%CI) 15.7 (11.5, 32.5) 20.0 (8.5, 24.4) 1.246 (0.621, 2.502)
34
LBA46: Efficacy and safety of poziotinib in treatment-naïve NSCLC harboring HER2 exon 20 mutations: a multinational phase 2 study (ZENITH20-4) – Cornelissen R, et al
• Study objective
– To evaluate the efficacy and safety of poziotinib in patients with EGFR or HER2 exon 20-mutated NSCLC in
the ZENITH20-4 study
Cornelissen R, et al. Ann Oncol 2021;32(suppl):Abstr LBA46
Primary endpoint
• ORR
Secondary endpoints
• DCR, DoR, safety
Key patient inclusion criteria
• EGFR or HER2 exon 20
insertion
• Treatment naïve/previously
treated
Poziotinib 16 mg/daya
(n=48)
Cohort 1: Previously treated; EGFR
exon 20 insertion NSCLC
Cohort 3: Treatment naïve; EGFR
exon 20 insertion NSCLC
Cohort 5: Exploratory of Cohorts 1–4
Cohort 2: Previously treated; HER2
exon 20 insertion NSCLC
Cohort 7: Atypical EGFR or HER2
mutation
Cohort 6: EGFR osimertinib failure
Cohort 4: Treatment naïve; HER2
exon 20 insertion NSCLC
aDose reduced to 8 mg BID for patients still enrolling
35
LBA46: Efficacy and safety of poziotinib in treatment-naïve NSCLC harboring HER2 exon 20 mutations: a multinational phase 2 study (ZENITH20-4) – Cornelissen R, et al
• Key results
Cornelissen R, et al. Ann Oncol 2021;32(suppl):Abstr LBA46
Poziotinib 16 mg/day
(n=48)
ORR, n (%) [95%CI] 21 (43.8) [29.5, 58.8]
BOR, n (%)
CR 1 (2.1)
PR 20 (41.7)
SD 15 (31.3)
PD 7 (14.6)
NE 5 (10.4)
DCR, n (%) 36 (75.0)
mPFS, mo (range) 5.6 (0–20.2+)
PFS duration, %
>6 months
>12 months
42
26
Duration of response
Su
rviv
al p
rob
ab
ility
1.0
0.8
0.6
0.4
0.2
0
Time, months
211815129630
0114572021No. at risk
Censored
mDoR, mo (range) 5.4 (2.8–19.1+)
Median follow-up of response, mo 13.5
Response duration, %
>6 months
>12 months
42
24
36
LBA46: Efficacy and safety of poziotinib in treatment-naïve NSCLC harboring HER2 exon 20 mutations: a multinational phase 2 study (ZENITH20-4) – Cornelissen R, et al
• Key results (cont.)
• Conclusions
– In patients with NSCLC and HER2 exon 20 mutations, 1L poziotinib demonstrated promising antitumor
activity and had a manageable safety profile
Cornelissen R, et al. Ann Oncol 2021;32(suppl):Abstr LBA46
AEs, n (%) Any grade Grade 3
Diarrhoea 40 (83) 7 (15)
Rash 34 (69) 17 (35)
Stomatitis/mucosal inflammation 39 (81) 10 (21)
Paronychia 22 (46) 4 (8)
Pneumonitis 2 (4) 1 (2)
TRAEs, n (%)Poziotinib 16 mg/day
(n=48)
Any 48 (100)
Serious 5 (10)
Led to interruption 42 (88)
Led to dose reduction 37 (77)
Led to discontinuation 6 (13)
37
LBA50: A randomized phase III study comparing cisplatin-pemetrexed (cis-pem) with carboplatin (C)-paclitaxel (P)-bevacizumab (B) in chemotherapy naïve patients (pts) with advanced KRAS mutated non-small cell lung cancer (NSCLC): NVALT22 – Dingemans AC, et al
• Study objective
– To evaluate the efficacy and safety of carboplatin + paclitaxel + bevacizumab in patients with advanced,
KRAS-mutated NSCLC compared with standard of care in the NVALT22 study
Dingemans AC, et al. Ann Oncol 2021;32(suppl):Abstr LBA50
Primary endpoint
• PFS
Secondary endpoints
• ORR, DCR, OS, safety
R
1:1
Pemetrexed
maintenance
Bevacizumab
maintenance
Stratification
• KRAS mutation (G12C vs. G12V vs. other)
• ECOG PS (0–1 vs. 2)
• Brain metastasis (yes vs. no)
• Prior anti-PD-L1 (yes vs. no)
Key patient inclusion criteria
• Advanced NSCLC
• KRAS mutation
• Chemotherapy naïve/previous
anti-PD-L1 therapy allowed
• ECOG PS 0–2
(n=240)Cisplatin 75 mg/m2 +
pemetrexed 500 mg/m2 q3w
(n=101)
Carboplatin AUC6 + paclitaxel 200 mg/m2 +
bevacizumab 15 mg/kg q3w
(n=102)
38
LBA50: A randomized phase III study comparing cisplatin-pemetrexed (cis-pem) with carboplatin (C)-paclitaxel (P)-bevacizumab (B) in chemotherapy naïve patients (pts) with advanced KRAS mutated non-small cell lung cancer (NSCLC): NVALT22 – Dingemans AC, et al
• Key results
Dingemans AC, et al. Ann Oncol 2021;32(suppl):Abstr LBA50
PFS
Su
rviv
al p
rob
ab
ility
, %
100
75
50
25
0
Time, months
60544842363024181260
0
(10)
1
(9)
1
(9)
1
(9)
1
(9)
1
(9)
2
(8)
4
(8)
9
(8)
39
(6)
102
(0)
0
(9)
0
(9)
0
(9)
0
(9)
1
(8)
2
(8)
4
(8)
7
(7)
8
(7)
35
(5)
101
(0)
CPB
Cis-Pem
Events = 184
Stratified HR 0.96 (95%CI 0.70, 1.31); p=0.81
mPFS CPB 5.2 mo (95%CI 4.4, 6.2)
mPFS Cis-Pem 4.7 mo (95%CI 3.9, 5.9)
CPB
Cis-Pem
No. at risk
(censored)
39
LBA50: A randomized phase III study comparing cisplatin-pemetrexed (cis-pem) with carboplatin (C)-paclitaxel (P)-bevacizumab (B) in chemotherapy naïve patients (pts) with advanced KRAS mutated non-small cell lung cancer (NSCLC): NVALT22 – Dingemans AC, et al
• Key results (cont.)
• Conclusions
– In patients with advanced KRAS-mutated NSCLC, carboplatin + paclitaxel + bevacizumab failed to
demonstrate improved PFS compared with cisplatin + pemetrexed and had a safety profile similar to
previous findings
Dingemans AC, et al. Ann Oncol 2021;32(suppl):Abstr LBA50
Grade ≥3 TRAEs occurring
in ≥5% of patients, %
CPB
(n=100)
Cis-Pem
(n=98)
All
(n=198) p-value
Neutropenia 6 8 14 0.59
Infection 5 2 7 0.44
Hypertension 7 0 7 0.01
Nausea 2 4 6 0.44
Malaise 2 1 3 1
40
LBA51: EMPOWER-Lung 3: cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small-cell lung cancer (NSCLC) – Gogishvili M, et al
• Study objective
– To evaluate the efficacy and safety of 1L cemiplimab + platinum-based chemotherapy in patients with
stage III/IV NSCLC without actionable mutations in the EMPOWER-Lung 3 study
Gogishvili M, et al. Ann Oncol 2021;32(suppl):Abstr LBA51
Primary endpoint
• OS
Secondary endpoints
PFS, ORR, DoR, BOR, PROs, safety
R
2:1
PD or 108
weeks
Key patient inclusion criteria
• Advanced, squamous/non-
squamous NSCLC (stage
IIIB/C–IV)
• Treatment-naïve
• No EGFR, ALK or ROS1
mutations
• Brain mets allowed if stable
• ECOG PS 0–1
(n=466)
Placebo +
platinum-doublet chemotherapya q3w
(4 cycles)
(n=152)
Cemiplimab 350 mg +
platinum-doublet chemotherapya q3w
(4 cycles)
(n=312)
aInvestigator choice; pemetrexed maintenance mandatory for patients with non-squamous
NSCLC who received a pemetrexed-containing regimen
Stratification
• PD-L1 expression (<1% vs. 1–49% vs ≥50%)
• Histology (non-squamous vs. squamous)
41
LBA51: EMPOWER-Lung 3: cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small-cell lung cancer (NSCLC) – Gogishvili M, et al
• Key results
Gogishvili M, et al. Ann Oncol 2021;32(suppl):Abstr LBA51
Overall survival
Patients,
n
Events,
n (%)
mOS, mo
(95%CI)
Cemiplimab + chemo 312 132 (42.3) 21.9 (15.5, NE)
Placebo + chemo 154 82 (53.2) 13.0 (11.9, 16.1)
Pro
ba
bili
ty o
f O
S
1.0
0.8
0.6
0.4
0.2
0
26242220181614121086420
No. at risk
008185286131162199233256269289312
Time, months
0025142646658598112126141154
Cemiplimab +
chemotherapy
Placebo +
chemotherapy
12-mo OS, % (95%CI)
65.7 (59.9, 70.9)
vs.
56.1 (47.5, 63.8)
HR 0.71 (95%CI 0.53, 0.93); p=0.014
Progression-free survival
Pro
ba
bili
ty o
f P
FS
1.0
0.8
0.6
0.4
0.2
0
26242220181614121086420
000215275790113145194248280312
Time, months
0001161116243464106133154
12-mo PFS, % (95%CI)
38.1 (32.4, 43.8)
vs.
16.4 (10.5, 23.4)
HR 0.56 (9%%CI 0.44, 0.70); p<0.0001
Patients,
n
Events,
n (%)
mPFS, mo
(95%CI)
Cemiplimab + chemo 312 204 (65.4) 8.2 (6.4, 9.3)
Placebo + chemo 154 122 (79.2) 5.0 (4.3, 6.2)
No. at risk
Cemiplimab +
chemotherapy
Placebo +
chemotherapy
Median duration of follow-up (range): 16.4 mo (8.5–24.0)
42
LBA51: EMPOWER-Lung 3: cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small-cell lung cancer (NSCLC) – Gogishvili M, et al
• Key results (cont.)
Gogishvili M, et al. Ann Oncol 2021;32(suppl):Abstr LBA51
Cemiplimab + chemo Placebo + chemo OS
n OS events/ n patients n OS events/ n patients HR (95%CI)
All patients 132/312 82/154 0.71 (0.53, 0.93)
Age group <65 years 72/184 53/94 0.57 (0.40, 0.81)
≥65 years 60/128 29/60 0.88 (0.56, 1.37)
Gender Male 113/268 75/123 0.55 (0.41, 0.74)
Female 19/44 7/31 2.11 (0.89, 5.03)
Race White 116/267 76/138 0.67 (0.50, 0.89)
Non-white 16/45 6/16 0.79 (0.31, 2.02)
Histology Squamous 57/133 39/67 0.56 (0.37, 0.84)
Non-squamous 75/179 43/87 0.79 (0.54, 1.14)
PD-L1 level <1% 54/95 27/44 1.01 (0.63, 1.60)
1–49% 40/114 31/61 0.52 (0.32, 0.83)
≥50% 38/103 24/49 0.61 (0.37, 1.02)
ECOG PS 0 11/51 6/18 0.55 (0.20, 1.49)
1 119/259 75/134 0.69 (0.52, 0.92)
Region Europe 118/270 76/138 0.67 (0.50, 0.90)
Asia 14/42 6/16 0.72 (0.27, 1.88)
Brain metastasis Yes 11/24 5/7 0.42 (0.14, 1.26)
No 121/288 77/147 0.68 (0.51, 0.90)
Cancer stage Locally advanced 16/45 13/24 0.54 (0.25, 1.15)
Metastatic 116/267 69/130 0.69 (0.51, 0.93)
Smoking Smokers 115/269 75/130 0.61 (0.46, 0.82)
Never smokers 17/43 7/24 1.28 (0.53, 3.08)
0.1 1 10Cemiplimab + chemo better Placebo + chemo better
43
LBA51: EMPOWER-Lung 3: cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small-cell lung cancer (NSCLC) – Gogishvili M, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC, 1L cemiplimab + platinum-based chemotherapy demonstrated significant
clinical benefit and improvement in OS and PFS, with a manageable safety profile
Gogishvili M, et al. Ann Oncol 2021;32(suppl):Abstr LBA51
n (%)
Cemiplimab + chemo
(n=312)
Placebo + chemo
(n=153)
Median duration of
exposure, weeks
(range)
38.5 (1.4–102.6) 21.3 (0.6–95.0)
TEAEs Any grade Grade 3–5 Any grade Grade 3–5
Overall 299 (96) 136 (44) 144 (94) 48 (31)
Led to discontinuation 16 (5) 13 (4) 4 (3) 4 (3)
Led to death 19 (6) 19 (6) 12 (8) 12 (8)
n (%)
Cemiplimab + chemo
(n=312)
Placebo + chemo
(n=153)
TRAEs
Overall 275 (88) 90 (29) 129 (84) 28 (18)
Led to discontinuation 10 (3) 7 (2) 1 (1) 1 (1)
Led to death 4 (1) 4 (1) 1 (1) 1 (1)
irAEs
Overall 59 (19) 9 (3) - -
TRAEs 3 (1) 3 (1) - -
Led to discontinuation 1 (0.3) 1 (0.3) - -
44
1171MO: PACIFIC-R real-world study: treatment duration and interim analysis of progression-free survival in unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy – Girard N, et al
• Study objective
– To evaluate the efficacy and safety of durvalumab in patients with unresectable, stage III NSCLC in a real-life
setting in the PACIFIC-R study
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr 1171MO
Primary endpoint
• PFS, OS
Secondary endpoints
• DCR, safety
PD/
up to 5 years
Retrospective data collection from
medical records
Key patient inclusion criteria
• Unresectable stage III NSCLC
• Any PD-L1 status
• No PD following platinum-
based chemotherapy
(n=1399)
Durvalumab 10 mg/kg q2w
45
1171MO: PACIFIC-R real-world study: treatment duration and interim analysis of progression-free survival in unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy – Girard N, et al
• Key results
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr 1171MO
PACIFIC-R FAS
(n=1339)
PACIFIC trial (durvalumab arm)
(n=476)
Total events, n (%) 737 (52.7) 268 (56.3)
Progression per RECIST, n (%) 456 (32.6)
Progression per physician assessment, n (%) 170 (12.2)
Progression, assessment unknown, n (%) 30 (2.1)
Deaths in absence of progression, n (%) 81 (5.8)
mPFS, mo (95%CI) 21.7 (19.2, 24.5) 16.9 (13.0, 23.9)
PFS rate, %
12-mo 62.4 55.7
24-mo 48.2 45.0
46
1171MO: PACIFIC-R real-world study: treatment duration and interim analysis of progression-free survival in unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy – Girard N, et al
• Key results (cont.)
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr 1171MO
mPFS, mo (95%CI)
PD-L1 ≥1% 22.4 (18.7, 25.5)
PD-L1 <1% 16.3 (11.7, 23.2)
Inconsistenta 25.2 (14.0, 27.3)
93 68 60 49 27 2 0
Histology mPFS, mo (95%CI)
Non-squamous 25.3 (22.0, 26.9)
Squamous 14.7 (12.8, 19.0)
No. at risk
PD-L1 ≥1%
PD-L1 <1%
Inconsistenta
Pro
ba
bili
ty o
f P
FS
0
0.2
0.4
0.6
0.8
1.0
0 6 12 18 24 30 36
Time, months
701 556 430 349 145 24 0173 131 99 77 38 7 0
PD-L1
No. at risk
Non-squamous
Squamous
Pro
ba
bili
ty o
f P
FS
Time, months
882 689 564 464 220 30 0496 384 279 220 90 19 0
0
0.2
0.4
0.6
0.8
1.0
0 6 12 18 24 30 36
mPFS, mo (95%CI)
Stage IIIA 23.7 (20.2, 26.5)
Stage IIIB/C 19.2 (15.8, 24.2)
mPFS, mo (95%CI)
Concurrent 23.7 (20.1, 25.8)
Sequential 19.4 (12.4, 25.3)
0
0.2
0.4
0.6
0.8
1.0
No. at risk
Concurrent
Sequential
Time, months
1071 842 672 548 245 41 0200 151 111 91 45 2 0
0 6 12 18 24 30 36
Pro
ba
bili
ty o
f P
FS
CRT Type
0
0.2
0.4
0.6
0.8
1.0
Pro
ba
bili
ty o
f P
FS
Stage
No. at risk
Stage IIIA
Stage IIIB/C
Time, months
604 490 391 316 134 16 0714 533 413 337 165 29 0
0 6 12 18 24 30 36
aTested but not clearly reported
47
1171MO: PACIFIC-R real-world study: treatment duration and interim analysis of progression-free survival in unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy – Girard N, et al
• Key results (cont.)
• Conclusions
– In patients with unresectable stage III NSCLC, real-world data on the effect of durvalumab after
chemotherapy were consistent with those observed in the PACIFIC trial
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr 1171MO
FAS (n=1399)
Discontinuation
reason,
n (%)
Median time from
durvalumab start to
discontinuation,
months
Patient decision 20 (1.4) 6.1
AE 233 (16.7) 2.8
Completed treatment 659 (47.1) 12.0
Disease progression 377 (26.9) 5.1
Death 21 (1.5) 1.9
Pneumonitis/ interstitial lung
disease, n (%)
FAS
(n=1399)
Any 250 (17.9)
Mild 56 (4.0)
Moderate 118 (8.4)
Severe 41 (2.9)
Life-threatening or fatal 5 (0.4)
48
1281O: Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden–positive (bTMB+) patients (pts) with first line (1L) advanced/metastatic (m)NSCLC: results of the Blood First Assay Screening Trial (BFAST) phase 3 cohort C – Dziadziuszko R, et al
• Study objective
– To evaluate the use of blood-based TMB as a predictive biomarker for immunotherapy in patients with
NSCLC in the BFAST study
Dziadziuszko R, et al. Ann Oncol 2021;32(suppl):Abstr 1281O
Primary endpoint
• PFS (RECIST v1.1, investigator assessed)
Secondary endpoints
• OS, ORR, DoR, safety
R
1:1
PD/loss of
benefit
PD/loss of
benefit
Stratification
• ECOG PS (0 vs. 1)
• Histology (SQ vs. non-SQ)
• Tissue availability (yes vs. no)
• bTMB status (moderate [10–15] vs. high [≥16])
Key patient inclusion criteria
• Unresectable stage IIIB–IV
NSCLC
• bTMB positive (≥10% cut-off)
• No EGFR/ALK alterations
• ECOG PS 0–1
(n=472)Platinum-based chemotherapy
q3w (4 or 6 cycles)*
(n=146)
Atezolizumab 1200 mg q3w
(n=145)
*Maintenance pemetrexed permitted for patients with non-squamous NSCLC
49
1281O: Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden–positive (bTMB+) patients (pts) with first line (1L) advanced/metastatic (m)NSCLC: results of the Blood First Assay Screening Trial (BFAST) phase 3 cohort C – Dziadziuszko R, et al
• Key results
Dziadziuszko R, et al. Ann Oncol 2021;32(suppl):Abstr 1281O
PF
S, %
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
0
20
40
60
80
100
Time, monthsNo. at risk
Atezo 145 101 83 54 46 32 25 18 10 9 5 4 3 2 1
Chemo 146 113 81 38 15 11 6 3 3 1 0 0 0 0 0
PFS Atezo (n=145) Chemo (n=146)
Events, n (%) 119 (82) 124 (85)
mPFS, mo (95%CI) 4.5 (3.9, 5.6) 4.3 (4.2, 5.5)
Stratified HR (95%Cl); p-value 0.77 (0.59, 1.00); 0.053
OS
, %
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
0
20
40
60
80
100
Time, monthsNo. at risk
Atezo 145 131 109 93 81 67 55 44 33 29 20 14 7 4 1
Chemo 146 129 115 93 76 62 43 35 29 22 17 12 11 2 0
OS Atezo (n=145) Chemo (n=146)
Events, n (%) 82 (57) 88 (60)
mOS, mo (95%CI) 13.3 (6.6, 18.4) 10.3 (8.5, 13.8)
Stratified HR (95%Cl); p-value 0.87 (0.64, 1.17); 0.35
Atezo
Chemo
Atezo
Chemo
PFS and OS in the bTMB ≥16 population
50
1281O: Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden–positive (bTMB+) patients (pts) with first line (1L) advanced/metastatic (m)NSCLC: results of the Blood First Assay Screening Trial (BFAST) phase 3 cohort C – Dziadziuszko R, et al
• Key results (cont.)
• Conclusions
– In patients with NSCLC selected by bTMB, atezolizumab monotherapy showed no significant improvement in
PFS or OS compared with platinum-based chemotherapy
Dziadziuszko R, et al. Ann Oncol 2021;32(suppl):Abstr 1281O
AEs, n (%)Atezolizumab
(n=234)
Chemotherapy
(221)
Any grade, all cause
Grade 3/4
Grade 5
216 (92.3)
107 (45.7)
13 (5.6)
216 (97.7)
127 (57.5)
12 (5.4)
Any grade TRAE
Grade 3/4
Grade 5
138 (59.0)
43 (18.4)
0
194 (87.8)
102 (46.2)
3 (1.4)
Any grade serious AE
Serious TRAEs
104 (44.4)
27 (11.5)
82 (37.1)
32 (14.5)
Any grade led to discontinuation 23 (9.8) 44 (19.9)
Any grade AESI
Grade 3/4
95 (40.6)
29 (12.4)
58 (26.2)
10 (4.5)
AESI requiring corticosteroids 41 (17.5) 20 (9.0)
Advanced NSCLCNot radically treatable stage III and stage IV
Later lines
52
LBA45: Primary data from DESTINY-Lung01: a phase 2 trial of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non–small cell lung cancer (NSCLC) – Li BT, et al
• Study objective
– To evaluate the efficacy and safety of trastuzumab deruxtecan in patients with HER2-mutated NSCLC in the
DESTINY-Lung01 study
Li BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45
Primary endpoint
• ORR (ICR)
Secondary endpoints
• DCR, DoR, PFS, OS, safety
Cohort 1:
HER2-expressing (IHC3+ or IHC2+)
trastuzumab deruxtecan 6.4 mg/kg q3w
(n=90)
Key patient inclusion criteria
• Unresectable/metastatic non-
squamous NSCLC
• Relapsed/refectory to standard
treatment
• HER2 expressing or HER2-
activating mutation
• No prior HER2-targeted therapy
• CNS metastasis allowed
Cohort 2:
HER2-mutated
trastuzumab deruxtecan 6.4 mg/kg q3w
(n=91)
53
LBA45: Primary data from DESTINY-Lung01: a phase 2 trial of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non–small cell lung cancer (NSCLC) – Li BT, et al
• Key results
– Efficacy was consistently observed across subgroups including those with asymptomatic baseline CNS
metastases (18/33 patients; ORR 54.5 [95%CI 36.4, 71.9])
Li BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45
Trastuzumab deruxtecan (n=91)
Confirmed ORR, n (%) [95%CI] 50 (54.9) [44.2, 65.4]
BOR, n (%)
CR 1 (1.1)
PR 49 (53.8)
SD 34 (37.4)
PD 3 (3.3)
NE 4 (4.4)
DCR, n (%) [95%CI] 84 (92.3) [84.8, 96.9]
mDoR, mo (95%CI) 9.3 (5.7, 14.7)
Median follow-up, mo (range) 13.1 (0.7–29.1)
54
LBA45: Primary data from DESTINY-Lung01: a phase 2 trial of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non–small cell lung cancer (NSCLC) – Li BT, et al
• Key results (cont.)
Li BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45
Best percentage change of tumour size from baseline
Patients (n=85)
Kinase domain
Extracellular domain
40
20
0
–20
–40
–60
–80
–100Be
st p
erc
en
t ch
an
ge
fro
m b
ase
line
in s
um
of d
iam
ete
rs
2
1
2
0
I
2
0
I
2
0
I
8
S
2
0
I
8
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
1
9
S
8
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
1
9
S
2
0
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
8
S
2
0
I
2
0
I
1
9
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
1
9
S
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
2
0
I
8
SHER2 mutation
(exon and subtype)
HER2 mutation domain location
HER2 protein
expression
2
+
1
+
2
+
2
+
1
+
2
+
2
+
2
+
2 3
+
0 2
+
3
+
2
+
2
+
0 0 2
+
1
+
2
+
0 2
+
2
+
0 3
+
3
+
2
+
0 0 3
+
2
+
I
3
+
2
+
3
+
1
+
2
+
1
+
3
+
2
+
2
+
2
+
2
+
3
+
2
+
2
+
2
+
3
+
2
+
2
+
02
+
HER2 gene
amplification
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ + + _ + _ _ _ _ _ _ _ _ _ _ _ _ _ +_
Prior HER2 TKI therapy Y Y Y YYY Y Y Y Y Y Y
55
LBA45: Primary data from DESTINY-Lung01: a phase 2 trial of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non–small cell lung cancer (NSCLC) – Li BT, et al
• Key results (cont.)
Li BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45
Progression-free survival
Pro
po
rtio
no
f p
atie
nts
, %
100
80
60
40
20
0
181614121086420 26242220
791315151919212531394249556974838991 011111127
Time, monthsNo. at risk
mPFS 8.2 mo (95%CI 6.0, 11.9)
Overall survival
mOS 17.8 mo (95%CI 13.8, 22.1)100
80
60
40
20
0
Time, months
91 192225293646515865687075757782868889 5710131314151719 13 0
0 18161412108642 26242220 28 30
56
LBA45: Primary data from DESTINY-Lung01: a phase 2 trial of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non–small cell lung cancer (NSCLC) – Li BT, et al
• Key results (cont.)
– Any grade TEAE ILD/pneumonitis was reported in 26.4% of patients, 75% were grade 1/2 and 2.2% were
grade 5
– TEAE ILD and pneumonitis led to discontinuation in 5.5% and 13.2% of patients, respectively
• Conclusions
– In previously treated patients with HER2-mutated NSCLC, trastuzumab deruxtecan demonstrated
encouraging activity and was generally well-toleratedLi BT, et al. Ann Oncol 2021;32(suppl):Abstr LBA45
TRAEs occurring in ≥20% of all patients, n (%)
Trastuzumab deruxtecan (n=91)
Any grade Grade ≥3
Nausea 66 (72.5) 8 (8.8)
Fatigue 48 (52.7) 6 (6.6)
Alopecia 42 (46.2) 0
Vomiting 36 (39.6) 3 (3.3)
Neutropenia 32 (35.2) 17 (18.7)
Anaemia 30 (33.0) 9 (9.9)
Diarrhoea 29 (31.9) 3 (3.3)
Decreased appetite 27 (29.7) 0
Leukopenia 21 (23.1) 4 (4.4)
Constipation 20 (22.0) 0
TEAEs, n (%)Trastuzumab deruxtecan
(n=91)
Any 88 (96.7)
Grade ≥3 42 (46.2)
Serious 18 (19.8)
Led to discontinuation 23 (25.3)
Led to dose reduction 31 (34.1)
Led to death 2 (2.2)
57
LBA47: Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): final results of phase 3 Atalante-1 randomised trial – Besse B, et al
• Study objective
– To evaluate the efficacy and safety of the anticancer vaccine OSE-2101 in patients with advanced HLA-A2+
NSCLC in the Atalante-1 study
– The study was stopped early in April 2020 due to COVID-19 pandemic and a new population of interest was
defined which included patients with secondary resistance after sequential immunotherapy
Besse B, et al. Ann Oncol 2021;32(suppl):Abstr LBA47
Primary endpoint
• OS
Secondary endpoints
• DCR, safety
R
2:1
PD/toxicity
PD/toxicity
Stratification
• Histology (SQ vs. NSQ)
• Best response to 1L (CR/PR vs. SD/PD)
• Line rank of prior ICI (1L vs. 2L)
Key patient inclusion criteria
• Advanced NSCLC
• Failure on platinum-based
chemotherapy and ICI
• Brain mets allowed if
asymptomatic
• ECOG PS 0–1
(n=103)
Standard of care
(docetaxel or pemetrexed)
(n=39)
OSE-2101 q3w for 6 doses then
q8w to year 1 then q12w
(n=64)
58
LBA47: Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): final results of phase 3 Atalante-1 randomised trial – Besse B, et al
• Key results:
Besse B, et al. Ann Oncol 2021;32(suppl):Abstr LBA47
Overall survival in the new population of interest (post-hoc)
OS
pro
babili
ty
1.0
0.8
0.6
0.4
0.2
0
Time, months
3633302724211815129630
01446912203244597080
01235915242938
No. at risk
OSE-2101
SoC
Cut-off: 15 Jan 2021; median follow-up: 25 months
OSE-2101
(n=80)
SoC
(n=38)
Events, n (%) 61 (76) 34 (90)
mOS, mo (95%CI) 11.1 (8.6, 13.5) 7.5 (4.7, 10.3)
OSE-2101
SoC
HR 0.59 (95%CI 0.38, 0.91)
p-value stratified = 0.017
59
LBA47: Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): final results of phase 3 Atalante-1 randomised trial – Besse B, et al
• Key results (cont.)
• Conclusions
– In patients with advanced HLA-A2+ NSCLC, OSE-2011 showed an interesting signal of activity in a specific
post-hoc restrictive subgroup of the ITT (118/219) and was generally well-tolerated
– Prospective validation of the signal is mandated
Besse B, et al. Ann Oncol 2021;32(suppl):Abstr LBA47
OSE-2101
(n=80)
SoC
(n=38)
Patients with measurable
lesions at baseline78 38
6-month DCR rate, n (%) 19 (25) 9 (24)OR 1.09 (95%CI 0.43, 2.75);
p=0.87
Objective response, n (%) 6 (8) 7 (18)OR 0.33 (9%%CI 0.10, 1.11);
p=0.07
mPFS, months (95%CI) 2.7 (1.6, 2.8) 3.2 (2.6, 4.7)HR 1.20 (95%CI 0.8, 1.8);
p=0.40
TRAEs, n (%)OSE-2101
(n=79)
SoC
(n=37)
All 60 (76) 29 (78)
Grade 3–5 9 (11) 13 (35)
Serious 9 (11) 3 (8)
Led to discontinuation 0 0
Led to death 0 0
60
LBA49: Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): preliminary results from the phase 1 TROPION-PanTumor01 study – Garon EB, et al
• Study objective
– To evaluate the efficacy and safety of datopotamab deruxtecan in patients with advanced NSCLC who
progressed after prior treatment in the TROPION-PanTumor01 study
Garon EB, et al. Ann Oncol 2021;32(suppl):Abstr LBA49
Primary endpoints
• MTD, safety
Secondary endpoints
• Efficacy, PK
Datopotamab deruxtecan
4 mg/kg (n=50)
Datopotamab deruxtecan
6 mg/kg (n=50)
Key patient inclusion criteria
• Advanced or metastatic NSCLC
• Refractory to or relapsed on
standard treatment
• CNS metastasis allowed
• ECOG PS 0–1
(n=175)
Datopotamab deruxtecan
8 mg/kg (n=80)
Data-DXd 0.27
to 10 mg/kg q3w
AGA subset analysis
(n=34)
Dose escalation Dose expansion
61
LBA49: Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): preliminary results from the phase 1 TROPION-PanTumor01 study – Garon EB, et al
• Key results
Garon EB, et al. Ann Oncol 2021;32(suppl):Abstr LBA49
Patients
Data-Dxd
(n=34)
ORR, n (%) 12 (35)
BOR, n (%)
CR 0
PR 12 (35)
SD 14 (41)
Non-CR/PD 2 (6)
PD 2 (6)
NE 4 (12)
mDoR, mo (95%CI) 9.5 (3.3, NE)
80
60
40
20
0
–20
–40
–60
–80
Best change in SOD (BICR) and tumour genotype
a b b b
Be
st ch
an
ge
in S
OD
fro
m b
ase
line
, %
Dose level
4 mg/kg
6 mg/kg
8 mg/kg
Actionable
genomic
alterations
TK
I w/o
osi
TK
I w/o
osi
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I
TK
I
TK
I
TK
I w/o
osi
TK
I
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
Other
EGFRm
Prior TKI
TK
I inclo
si
No
No
TK
I inclo
si
TK
I inclo
si
TK
I
TK
I
TK
I inclo
si
TK
I inclo
si
TK
I inclo
si
Ex19del
Ex20in
s
G719s
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex19del
Ex20in
s
Ex20in
s
L858R
L858R
L858R
L858R
L858R
RO
S1
ALK
ALK
Negativ
e
Negativ
e
Unknow
n
ALK
L861Q
T790M
T790M
T790M
T790M
T7
90M
T7
90M
T7
90M
T7
90M
T7
90M
E700K
K714N
LM5R
T790M
E74G
aPateint NE; bpatients with unconfirmed PR
62
LBA49: Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): preliminary results from the phase 1 TROPION-PanTumor01 study – Garon EB, et al
• Key results (cont.)
• Conclusions
– In heavily pretreated patients with advanced NSCLC, datopotamab deruxtecan demonstrated clinical
antitumor activity across different genomic alterations including EGFR and had a manageable safety profile
Garon EB, et al. Ann Oncol 2021;32(suppl):Abstr LBA49
AEs, %
Datopotamab deruxtecan
(n=34)
TEAE 100
Grade ≥3 53
TRAEs 88
Grade ≥3 38
Serious TEAEs 35
Grade ≥3 29
AEs, %
Datopotamab deruxtecan
(n=34)
Dose adjustments
Led to discontinuation 15
Led to dose interruption 27
Led to dose reduction 15
Drug-related ILD 1
Grade ≤2 0
Grade 3/4 0
Grade 5 1
63
1191O: MRTX-500: phase 2 trial of sitravatinib (Sitra) + nivolumab (Nivo) in patients (pts) with nonsquamous (NSQ) non–small-cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy – Leal TA, et al
• Study objective
– To evaluate the efficacy and safety of 2L or 3L sitravatinib + nivolumab in patients with non-squamous
NSCLC in the MRTX-500 study
Leal TA, et al. Ann Oncol 2021;32(suppl):Abstr 1191O
Primary endpoint
• ORR (RECIST v1.1)
Secondary endpoints
• DoR, CBR, PFS, OS, safety
Key patient inclusion criteria
• Advanced non-squamous NSCLC
• No driver mutations
• Anti-PD-L1 last treatment line
• CR, PR or SD ≥12 weeks from
prior treatment
• No uncontrolled brain mets
• ECOG PS 0–2
(n=68)
Sitravatinib 120 mg/day +
nivolumab
(n=68)
64
1191O: MRTX-500: phase 2 trial of sitravatinib (Sitra) + nivolumab (Nivo) in patients (pts) with nonsquamous (NSQ) non–small-cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy – Leal TA, et al
• Key results (cont.)
Leal TA, et al. Ann Oncol 2021;32(suppl):Abstr 1191O
0 7 14 21 28 35 42
PRCR
PRSD
PDCR
SDPR
SDPR
PRPR
SDSD
SDSDSDSD
PRPR
SDSDSD
SDSD
SDSD
SDSD
PRSDSD
SDSDSD
SDSD
SDSD
PRSDSDSDSD
PDSD
SDSD
SDSD
PDSDPDSD
SDSDPD
SD
Duration of treatment (n=58)
Duration of treatment, months
Progression
First Response
Treatment Ongoing
Death
• ORR 18% (12/68), including 2 CRs (3%) and 10 PRs (15%)
– DCR 78% (53/68)
• mDoR 12.8 months
• Median duration of treatment:
– Sitravatinib: 4.8 mo (range: 0–40)
– Nivolumab: 5.2 mo (range: 0–41)
65
1191O: MRTX-500: phase 2 trial of sitravatinib (Sitra) + nivolumab (Nivo) in patients (pts) with nonsquamous (NSQ) non–small-cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy – Leal TA, et al
• Key results
Leal TA, et al. Ann Oncol 2021;32(suppl):Abstr 1191O
Progression-free survival (n=68)
100
80
60
40
20
00 6 12 18 24 30 36 42
31%
45%
79%
Time, months
PF
S, %
OS
, %
56%
45%
32%
0 6 12 18 24 30 36 42
100
80
60
40
20
0
Time, months
Overall survival (n=68)
Sitravatinib + nivolumab
(n=68)
mPFS, mo (95%Cl) 5.7 (4.9, 7.6)
Events/censored, n (%) 53 (78)/15 (22)
Sitravatinib + nivolumab
(n=68)
mOS, mo (95%Cl) 14.9 (9.3, 21.1)
Events/censored, n (%) 46 (68)/22 (32)
No. at risk 68 25 10 4 3 2 1 0 No. at risk 68 52 34 26 16 11 4 0
66
1191O: MRTX-500: phase 2 trial of sitravatinib (Sitra) + nivolumab (Nivo) in patients (pts) with nonsquamous (NSQ) non–small-cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy – Leal TA, et al
• Key results (cont.)
Leal TA, et al. Ann Oncol 2021;32(suppl):Abstr 1191O
TRAEs occurring in
≥15% of patients, %
Sitravatinib + nivolumab (n=68)
Any grade Grade 3/4
Any 93 66
Diarrhoea 62 16
Fatigue 52 4
Nausea 44 2
Hypertension 40 22
Decreased appetite 35 0
Weight decreased 31 9
Vomiting 31 0
Hypothyroidism 22 0
Dysphonia 19 0
ALT increased 18 2
AST increased 16 0
Stomatitis 15 2
PPE syndrome 15 3
Dehydration 15 3
TRAEs ≥15% of patients, %
Sitravatinib + nivolumab
(n=68)
Led to discontinuation 22
Sitravatinib 21
Nivolumab 9
Led to dose reduction of sitravatinib 60
80 mg 31
60 mg 22
40 mg 7
Led to ≥1 dose interruption of sitravatinib 81
67
1191O: MRTX-500: phase 2 trial of sitravatinib (Sitra) + nivolumab (Nivo) in patients (pts) with nonsquamous (NSQ) non–small-cell lung cancer (NSCLC) progressing on or after prior checkpoint inhibitor (CPI) therapy – Leal TA, et al
• Conclusions
– In patients with non-squamous NSCLC, sitravatinib + nivolumab provided interesting activity signals and
promising outcomes at IO resistance, and no new safety signals were reported
Leal TA, et al. Ann Oncol 2021;32(suppl):Abstr 1191O
68
1192MO: Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: analysis from the CHRYSALIS study – Leighl NB, et al
• Study objective
– To evaluate the efficacy and safety of amivantamab alone or combined with lazertinib after osimertinib failure
in patients with advanced, EGFR-mutant NSCLC P
Leighl NB, et al. Ann Oncol 2021;32(suppl):Abstr 1192MO
Primary endpoint
• ORR
Secondary endpoints
• DoR, PFS, OS, safety
Post-osimertinib
amivantamab
cohorta
(n=121) Key patient inclusion criteria
• Advanced NSCLC
• EGFR mutant
• Unresponsive to prior
treatmentCombination
Amivantamab
1050/1400 mg +
lazertinib 240 mg
or SOC chemo
Monotherapy
Amivantamab
1050/1400 mg
aMajor biomarker pre-selected (T790M+/-; C797S+/-;MET amplified; MET exon14
skipping; EGFR exon20 insertion); bbiomarker unselected
Post-osimertinib
amivantamab +
lazertinib cohortb
(n=45)
Post any EGFR TKI (T790M+, C797S+)
Post any EGFR TKI (T790M-, C797S-)
Post osimertinib (C797S+)
Post any EGFR TKI (MET amplified)
MET Exon 14 skipping
EGFR Exon20ins
AMI + LAZ
Post-osimertinib EGFRm NSCLC
AMI + SoC chemotherapy
Advanced NSCLC
69
1192MO: Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: analysis from the CHRYSALIS study – Leighl NB, et al
• Key results
– ORR was higher among those with identified EGFR/MET-based osimertinib resistance receiving
amivantamab + lazertinib then amivantamab alone (47% vs. 18%)
Leighl NB, et al. Ann Oncol 2021;32(suppl):Abstr 1192MO
Post-osimertinib amivantamab cohort
(n=121)
Post-osimertinib amivantamab + lazertinib cohort
(n=45)
BOR, % 27 36
Confirmed ORR, % (95%CI) 19 (12, 27) 36 (22, 51)
CR, n (%) 0 1 (2)
PR, n (%) 23 (19) 15 (33)
SD, n (%) 53 (44) 14 (31)
PD, n (%) 39 (32) 11 (24)
NE, n (%) 6 (5) 4 (9)
mDoR, months (95%CI) 5.9 (4.2, 12.6) 9.6 (5.3, NE)
CBR, % (95%CI) 48 (39, 57) 64 (49, 78)
mPFS, months (95%CI) 4.2 (3.2, 5.3) 4.9 (3.7, 9.5)
mF/U (range) 6.9 (0.7–38.6) 11.1 (1.0–15.0)
70
1192MO: Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: analysis from the CHRYSALIS study – Leighl NB, et al
• Key results (cont.)
• Conclusions
– In patients with advanced EGFR-mutant NSCLC, amivantamab + lazertinib may have higher antitumor
activity than amivantamab alone with a safety profile consistent with previous findings
Leighl NB, et al. Ann Oncol 2021;32(suppl):Abstr 1192MO
TEAEs occurring in ≥20% with
amivantamab monotherapy, n (%)
Amivantamab
(n=121)
Amivantamab + lazertinib cohort
(n=45)
Infusion-related reaction 83 (69) 35 (78)
Paronychia 45 (37) 22 (49)
Acneiform dermatitis 34 (28) 23 (51)
Hypoalbuminemia 31 (26) 17 (38)
Rash 32 (26) 12 (27)
Constipation 31 (26) 12 (27)
Nausea 29 (24) 20 (44)
Dyspnoea 28 (23) 11 (24)
Pruritus 27 (22) 14 (31)
71
1193MO: Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): preliminary results from CHRYSALIS-2 – Shu CA, et al
• Study objective
– To evaluate the efficacy and safety of amivantamab alone or in combination with lazertinib in patients with
advanced, EGFR-mutant NSCLC
Shu CA, et al. Ann Oncol 2021;32(suppl):Abstr 1193MO
Primary endpoint
• ORR
Secondary endpoints
• CBR, DoR, PFS, OS, safety
Key patient inclusion criteria
• Advanced NSCLC
• EGFR Exon19del or L858R
(n=136)
Amivantamab
1050/1400 mg +
lazertinib 240 mgPlatinum-based
chemotherapy, osimertinib
or other (any number of prior
lines, any sequence)
Osimertinib (1L or 2L with
prior 1st/2nd gen EGFR TKI)
with platinum-based
chemotherapy as last line
Heavily pretreated
(n=56)
Target (3L/4L)
(n=80)
72
1193MO: Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): preliminary results from CHRYSALIS-2 – Shu CA, et al
• Key results
Shu CA, et al. Ann Oncol 2021;32(suppl):Abstr 1193MO
NE NE
60
40
20
0
-20
-40
-60
-80
-100
PR SD PD
Best overall response in target populationa (n=29)
Ch
an
ge
fro
m b
ase
line in
So
Do
f ta
rge
t le
sio
ns,
% PR SD PD
Best overall response in heavily treated populationb (n=47)
60
40
20
0
-20
-40
-60
-80
-100
PD PD NE PDSD
CR
ORR 41% (95%CI 24, 61)
CBR 69% (95%CI 49, 85)
Median follow-up 4.6 mo (range 0.4–9.6)
ORR 21% (95%CI 11, 36)
CBR 51% (95%CI 36, 66)
Median follow-up 4.5 mo (range 0.3–9.7)
aPrevious treatment: 1/2L osimertinib + 1/2L EGFR TKI followed by platinum-based
chemotherapy; bno restrictions to prior treatment lines
Post-osimertinib amivantamab + lazertinib (n=136)
73
1193MO: Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): preliminary results from CHRYSALIS-2 – Shu CA, et al
• Key results (cont.)
– Grade ≥3 TRAEs occurred in 50 (37%) patients, with the most common being infusion-related reaction (9%)
and dyspnoea (6%)
– Pneumonitis/ILD occurred in 4 (3%) patients
– AEs led of dose discontinuation (11%), dose reduction (18%) and dose interruption (46%)
• Conclusions
– In pretreated patients with advanced EGFR-mutant NSCLC, amivantamab + lazertinib demonstrated
favourable antitumor activity and was generally well-tolerated with no new safety signals reported
Shu CA, et al. Ann Oncol 2021;32(suppl):Abstr 1193MO
74
1194MO: Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results – Paz-Ares L, et al
• Study objective
– To evaluate the efficacy and safety of canakinumab (a monoclonal anti-IL-1β antibody) + docetaxel in
patients with advanced NSCLC in the CANOPY-2 study
Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr 1194MO
Primary endpoint
• OS
Secondary endpoints
• PFS, ORR, DCR, DoR, PRO, safety
R
1:1
PD/
toxicity/
withdrawal
PD/
toxicity/
withdrawal
Stratification
• Histology (SQ vs. non-SQ)
• Best response to 1L (CR/PR vs. SD/PD)
• Line rank of prior ICI (1L vs. 2L)
Key patient inclusion criteria
• Stage IIIB–IV, squamous or non-
squamous NSCLC
• Prior chemotherapy + anti-PD-L1
• No EGFR or ALK mutations
• ECOG PS ≤1
(n=237)Placebo +
docetaxel 75 mg/m2 q3w
(n=117)
Canakinumab 200 mg q3w
+ docetaxel 75 mg/m2
(n=120)
75
1194MO: Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results – Paz-Ares L, et al
• Key results
Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr 1194MO
Overall survival Progression-free survival
Eve
nt-
fre
e p
rob
ab
ility
1.00
0.75
0.50
0.25
0
181614121086420
Time, monthsNo. at risk
(no. of events)0
(73)
6
(72)
18
(69)
32
(65)
49
(55)
70
(47)
83
(34)
95
(23)
109
(9)
120
(0)
0
(68)
9
(67)
17
(62)
32
(60)
50
(51)
66
(43)
80
(31)
91
(20)
104
(7)
117
(0)
Can + Dtx
PBO + Dtx
6-mo OS
71% vs. 72%
12-mo OS
41% vs. 42%
mOS
10.5 vs. 11.3 mo
HR 1.06
(95%CI 0.76, 1.48)
One-sided p-value=0.63
Can + Dtx (n=120)
PBO + Dtx (n=117)
Eve
nt-
fre
e p
rob
ab
ility
1.00
0.75
0.50
0.25
0
1614121086420
Time, months
0
(100)
1
(100)
4
(99)
7
(98)
13
(95)
28
(81)
62
(51)
87
(27)
120
(0)
1
(94)
2
(94)
8
(91)
12
(88)
20
(83)
35
(71)
60
(47)
77
(31)
117
(0)
6-mo PFS
27% vs. 34%
12-mo PFS
8% vs. 12%
mPFS
4.2 vs. 4.2 mo
HR 1.12
(95%CI 0.85, 1.50)
Can + Dtx (n=120)
PBO + Dtx (n=117)
76
1194MO: Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results – Paz-Ares L, et al
• Key results (cont.)
• Conclusions
– In patients with advanced NSCLC, the addition of canakinumab to chemotherapy did not provide
improvement in OS and PFS over chemotherapy alone and the safety profile was comparable to previous
findings
Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr 1194MO
Canakinumab + docetaxel Placebo + docetaxel
AEs, n (%) Any grade Grade 3/4 Grade 5 Any grade Grade 3/4 Grade 5
Any grade 114 (95.0) 74 (61.7) 10 (8.3) 112 (98.2) 73 (64.0) 6 (5.3)
TRAEs 105 (87.5) 61 (50.8) 3 (2.5) 97 (85.1) 48 (42.1) 1 (0.9)
Serious AEs 55 (45.8) 41 (34.2) 10 (8.3) 50 (43.9) 39 (34.2) 6 (5.3)
Serious TRAEs 30 (25.0) 24 (20.0) 3 (2.5) 21 (18.4) 19 (16.7) 1 (0.9)
Led to discontinuation 28 (23.3) 11 (9.2) 7 (5.8) 33 (28.9) 12 (10.5) 3 (2.6)
Led to canakinumab/placebo discontinuation 16 (13.3) 8 (6.7) 7 (5.8) 12 (10.5) 6 (5.3) 3 (2.6)
AEs of special interest
Infections 59 (49.2) 18 (15.0) 8 (6.7) 47 (41.2) 18 (15.8) 2 (1.8)
Neutropenia 51 (42.5) 42 (35.0) 0 49 (43.0) 44 (38.6) 0
Thrombocytopenia 27 (22.5) 3 (2.5) 1 (0.8) 26 (22.8) 2 (1.8) 1 (0.9)
Other malignancies
SCLC, mesothelioma and thymic epithelial tumors
78
LBA61: Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase 3 CASPIAN study – Paz-Ares L, et al
• Study objective
– To evaluate the efficacy and safety of 1L etoposide + cisplatin/carboplatin ± durvalumab ± tremelimumab in
patients with ES-SCLC in the CASPIAN study
Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr LBA61
Primary endpoint
• OS
Secondary endpoints
• PFS, ORR, PROs, safety
Durvalumab 1500 mg + tremelimumab 75 mg
+ etoposide-platinum* q3w (4 cycles)
(n=268)
R
1:1:1
Etoposide-platinum* q3w (up to 6 cycles)
(n=269)
Durvalumab 1500 mg +
etoposide-platinum* q3w (4 cycles)
(n=268)Key patient inclusion criteria
• ES-SCLC
• Treatment naïve
• Asymptomatic/stable CNS
metastases
• WHO PS 0–1
(n=805; 414 for HLA-I/II genotyping)
PD
PD
Durvalumab
1500 mg q4w
Durvalumab
1500 mg q4w
Optional PCI
Stratification
• Platinum agent (carboplatin vs. cisplatin)
*Etoposide 80–100 mg/m2 + carboplatin AUC5–6 or cisplatin 75–80 mg/m2
79
LBA61: Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase 3 CASPIAN study – Paz-Ares L, et al
• Key results
Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr LBA61
3-year overall survival update: D + EP vs. EP
D + EP EP
Events 221/268 (82.5) 248/269 (92.9)
mOS, mo (95%CI) 12.9 (11.3, 14.7) 10.5 (9.3, 11.2)
HR (95%CI) 0.71 (0.60, 0.86)
Nominal p-value 0.0003
Median follow-up in censored patients:
39.4 months (range 0.1–47.5)
OS
pro
ba
bili
ty
1.0
0.8
0.6
0.4
0.2
0
Time, months
51484542393633302724211815129630
No. at risk
003132539465054607085109140177214244268
0003101317192436516482104156212243269
D + EP
EP
52.8%
32.0%22.9%
17.6%
5.8%13.9%
24.8%39.3%
3-year overall survival update: D + T + EP vs. EP
D + T + EP EP
Events 226/268 (84.3) 248/269 (92.2)
mOS, mo (95%CI) 10.4 (9.5, 12.0) 10.5 (9.3, 11.2)
HR (95%CI) 0.81 (0.67, 0.97)
Nominal p-value 0.0200
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
0
0.2
0.4
0.6
0.8
1.0
43.5%
30.6%22.9%
15.3%39.3%
24.8%
13.9%5.8%
D + T + EP 268 238 200 156 114 92 80 70 60 56 48 41 37 26 11 2 0
EP 269 243 212 156 104 82 64 51 36 24 19 17 13 10 3 0 0
Median follow-up in censored patients:
39.4 months (range 0.1–47.5)
Time, months
OS
pro
ba
bili
ty
No. at risk
80
LBA61: Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase 3 CASPIAN study – Paz-Ares L, et al
• Key results (cont.)
• Conclusions
– In patients with ES-SCLC, 1L durvalumab + etoposide + cisplatin/carboplatin continued to demonstrate
survival benefit without any new safety concerns
Paz-Ares L, et al. Ann Oncol 2021;32(suppl):Abstr LBA61
TRAEs, n (%)
D + EP
(n=265)
D + T + EP
(n=266)
EP
(n=266)
Serious AE 86 (32.5) 126 (47.4) 97 (36.5)
Febrile neutropenia 12 (4.5) 11 (4.1) 12 (4.5)
Pneumonia 6 (2.3) 16 (6.0) 11 (4.1)
Anaemia 5 (1.9) 9 (3.4) 12 (4.5)
Thrombocytopenia 1 (0.4) 6 (2.3) 9 (3.4)
Hyponatremia 2 (0.8) 9 (3.4) 4 (1.5)
Neutropenia 2 (0.8) 5 (1.9) 7 (2.6)
Diarrhoea 2 (0.8) 7 (2.6) 4 (1.5)
Pulmonary embolism 1 (0.4) 7 (2.6) 0
Led to death 14 (5.3) 29 (10.9) 16 (6.0)
TRAEs led to death 6 (2.3) 12 (4.5) 2 (0.8)
81
LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al
• Study objective
– To evaluate the long-term efficacy and safety of nivolumab + ipilimumab in patients with unresectable
malignant pleural mesothelioma in the CheckMate 743 study
Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65
Cisplatin or carboplatin + pemetrexed q3w
(6 cycles)
(n=302)
R
1:1
Nivolumab 3 mg/kg q2w +
ipilimumab 1mg/kg q6w (up to 2 years)
(n=303)Key patient inclusion criteria
• Unresectable MPM
• Treatment naïve
• ECOG PS 0–1
(n=605)
PD, toxicity
or 2 years
follow-up
Stratification
• Histology (epithelioid vs non-epithelioid)
• Gender
Primary endpoint
• OS
Secondary endpoints
• ORR, DCR, PFS (BICR), safety, biomarker analysis
82
LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al
• Key results (cont.)
Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65
NIVO + IPI
(n=303)
Chemo
(n=302) HR (95%CI)
mOS, mo 18.1 14.1 0.73 (0.61, 0.87)
mPFS, mo 6.8 7.2 0.92 (0.76, 1.11)
ORR, % 39.6 44.0
mDoR, mo 11.6 6.7
OS
, %
100
80
60
40
20
0
No. at risk Time, months
51 54484542393633302724211815129630
3-year update: overall survival in all randomized patients
2 0718354962738097116126145173200226251273303
0 06112033434654697697114138164192234269302
NIVO + IPI
Chemo
68%
41%
23%
58%
27%
15%
NIVO + IPI
Chemo
83
LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al
• Key results (cont.)
Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65
Epithelioid Non-epithelioid
NIVO + IPI
(n=229)
Chemo
(n=226)
mOS, mo 18.2 16.7
HR (95%Cl) 0.85 (0.69, 1.04)
NIVO + IPI
(n=74)
Chemo
(n=76)
mOS, mo 18.1 8.8
HR (95%Cl) 0.48 (0.34, 0.69)
OS
, %
100
80
60
40
20
0
0 6 12 18 24 30 36 42 48 54
Time, months
229 192 154 111 90 63 48 29 4 0NIVO + IPI
No. at risk
226 182 141 101 69 50 40 18 5 0Chemo
69%
66%
42%
33% 24%
19%
NIVO + IPI
Chemo
OS
, %
100
80
60
40
20
0
0 6 12 18 24 30 36 42 48 54
Time, months
74 59 46 34 26 17 14 6 3 0NIVO + IPI
No. at risk
76 52 23 13 7 4 3 2 1 0Chemo
63%
38%
22%NIVO + IPI
Chemo4%10%
33%
84
LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al
• Key results
Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65
NIVO + IPI
Low
(n=82)
High
(n=83)
mOS, mo 16.8 21.8
HR (95%CI) 0.57 (0.40, 0.82)
OS
, %
100
80
60
40
20
0
No. at risk Time, months
544842363024181260
01811142331486582
021124313846597283
Low
High
74%
49%
35%60%
30%
15%
Low
High
100
80
60
40
20
0
Time, months
544842363024181260
01611152338506482
0038111823366380
61%
28%
13%
46%
24%
11%
Low
High
OS
, %
Chemo
Low
(n=82)
High
(n=83)
mOS, mo 15.2 11.6
HR (95%CI) 1.14 (0.82, 1.59)
Overall survival by 4-gene inflammatory signature scorea
aIncluding CD8A, STAT1, LAG3, CD274 (PD-L1) genes
85
LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al
• Key results (cont.)
Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65
mOS, monthsUnstratified
HRSubgroup NIVO + IPI Chemo
Tissue TMB tertile
Low (n=103) 19.3 18.0 0.74
Intermediate (n=97) 17.9 9.9 0.48
High (n=95) 17.1 14.1 0.70
LIPI score
Good (n=293) 21.6 16.3 0.78
Intermediate (n=233) 17.1 14.1 0.76
Poor (n=47) 6.1 6.0 0.83
86
LBA65: First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743 – Peters S, et al
• Key results (cont.)
• Conclusions
– In patients with MPM, 1L nivolumab + ipilimumab demonstrated long-term benefit up to 3 years, irrespective
of histology, and had a favourable safety profile
– High 4-gene inflammatory signature and LIPI scores correlated with improved survival benefit for nivolumab +
ipilimumab
Peters S, et al. Ann Oncol 2021;32(suppl):Abstr LBA65
NIVO + IPI (n=300) Chemo (n=284)
TRAEs, % Any grade Grade 3/4 Any grade Grade 3/4
Any grade 80 31 82 32
Led to any treatment component discontinuation 23 15 16 7
Led to all treatment discontinuation 17 13 8 5
Serious 21 16 8 6
Led to death 1 <1
87
1732MO: Pembrolizumab and nintedanib for patients with advanced mesothelioma– Danios FX, et al
• Study objective
– To evaluate the efficacy and safety of nintedanib + pembrolizumab in patients with advanced malignant
mesothelioma
Danios FX, et al. Ann Oncol 2021;32(suppl):Abstr 1732MO
Key patient inclusion criteria
• Advanced pleural
mesothelioma
• Relapsed after platinum-
based chemotherapy
(n=30)
Nintedanib 150 mg BID
(n= 30)PD
Blood and tumour sample were
taken during treatment
Nintedanib 150 mg BID
+ pembrolizumab
200 mg q3w
(n= 30)
Induction Maintenance
88
1732MO: Pembrolizumab and nintedanib for patients with advanced mesothelioma– Danios FX, et al
• Key results
Danios FX, et al. Ann Oncol 2021;32(suppl):Abstr 1732MO
60
40
20
0
–20
–40
–60
–80
–100
Ch
an
ge
fro
m b
ase
line
, %
Best objective response
PD
SD
PR
DCR at 12 weeks 68.4%
(95%CI 43.4, 87.4)
IHC
PD-L1+ on tumour cells surface
Pe
rcen
tage
40
30
20
10
0No DCB DCB
BOR
PD
SD
PR
38
40
62
63
19
23
15
Pe
rcen
tage a
mo
ng
tota
l ce
lls
No DCB DCB
15
10
5
0
56
19
4045
Total CD45+
immune cells
No DCB DCB
6
4
2
0
19
4016
Total CD3+
T cells
55
30
Flow cytometry
Pe
rcen
tage a
mo
ng
CD
3+
ce
lls
No DCB DCB
15
10
5
0
56
55
Total CD8+
T cells
40
225018
55
3044
89
1732MO: Pembrolizumab and nintedanib for patients with advanced mesothelioma– Danios FX, et al
• Key results (cont.)
– The most common grade 3 AEs occurring in ≥5% of patients were fatigue (6.7%), dyspnoea (6.7%), skin
disorder (6.7%) and increased lipase (6.7%)
– Grade 5 myocarditis and cardiac disorder occurred in 1 (3%) patient
• Conclusions
– In patients with unresectable advanced MPM, nintedanib + pembrolizumab showed activity and had a
manageable safety profile
– Baseline tumour levels of PD-L1 and CD8+ T-cells were predictive of treatment response
Danios FX, et al. Ann Oncol 2021;32(suppl):Abstr 1732MO
90
LBA66: Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial – Girard N, et al
• Study objective
– To evaluate the efficacy and safety of 2L nivolumab with or without ipilimumab in patients with advanced type
B3 thymoma or thymic carcinoma in the NIVOTHYM study
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr LBA66
Cohort 2
Nivolumab 240 mg q2w +
ipilimumab 1mg/kg q6w
Cohort 1
Nivolumab 240 mg q2w
(n=49)Key patient inclusion criteria
• Advanced/relapsed type B3
thymoma or thymic carcinoma
• Prior platinum-based
chemotherapy
(n=55)
Primary endpoint
• 6-month PFS rate (RECIST v1.1)
Secondary endpoints
• ORR, DCR, PFS, OS, safety
91
LBA66: Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial – Girard N, et al
• Key results
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr LBA66
NIVO (n=49)
n (%) By central review By local investigator
6-mo PFS rate
Success 17 (35) 19 (39)
Failure 32 (65) 30 (61)
95%CI 22, 50 25, 54
80%CI 26, 45 29, 49
Reason for failure
PD 24 24
Death without PD before 6 months 3 3
Start of new treatment before PD 1 -
Unknown disease status 4 3
92
LBA66: Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial – Girard N, et al
• Key results (cont.)
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr LBA66
NIVO (n=49)
BOR (investigator), n (%)
PR 6 (12)
SD 25 (51)
PD 13 (27)
NE 5 (10)
Response rate (CR + PR), % (95%CI) 12 (5, 25)
DCR (CR + PR + SD), % (95%CI) 63 (48, 77)
93
LBA66: Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial – Girard N, et al
• Key results (cont.)
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr LBA66
Progression-free survival Overall survival
Events/total mPFS, mo (95%CI)
34/49 6.0 (3.1, 10.4)
PF
S, %
100
80
60
40
20
0
Time, months242220181614121086420
No. at risk 1344679141723263449
OS
, %
100
80
60
40
20
0
Time, months
mOS, mo (95%CI)
21.3 (11.6, NE)
2826242220181614121086420
No. at risk 012479131518253039434749
94
LBA66: Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial – Girard N, et al
• Key results (cont.)
– Grade 4/5 AEs included respiratory failure, neutropenia, myocarditis, immune-mediated transaminitis, sepsis
and dyspnoea
• Conclusions
– In patients with advanced type B3 thymoma or thymic carcinoma, 2L nivolumab monotherapy showed
survival benefit although failed to meet the primary endpoint for 6-month PFS rate
– The second cohort investigating nivolumab + ipilimumab combination is ongoing
Girard N, et al. Ann Oncol 2021;32(suppl):Abstr LBA66
Nivolumab (n=54)
n (%) Grade ≥1 Grade ≥3 Grade 4 Grade 5
All AEs 54 (100) 32 (59) 5 (9) 1 (2)
TRAEs 44 (81) 14 (26) 4 (7) -
Recommended