Patient disposition• The study was completed on May 27, 2020 (last patient last visit), with 61 patients in phase 1b and 100

patients in phase 2

• Out of the 161 patients who discontinued from treatment phase, 130 patients (80.7%) entered thesurvival follow-up and 31 patients (19.3%) discontinued from study (Table 1)

– Four patients alive at the end of the study and 1 patient was transferred into a rollover clinical study

• Most common reason for discontinuation of study treatment was disease progression (123 patients,76.4%), followed by adverse events (AEs, 19 patients, 11.8%)

Table 1: Patient Disposition

CharacteristicAll patients

(N=161)n (%)

Treatment phase

Completed 6 cycles of treatment 70 (43.5)

Discontinued from treatment phase 161 (100)

Entered survival follow-up 130 (80.7)

Discontinued from study 31 (19.3)

Primary reason for discontinuation from treatment

Progressive disease 123 (76.4)

Adverse event 19 (11.8)

Subject/guardian decision 8 (5.0)

Death 7 (4.3)

Non-compliance with study treatment 1 (0.6)

Physician decision 1 (0.6)

Protocol deviation 1 (0.6)

Study terminated by sponsor 1 (0.6)

Baseline characteristics• The majority of patients were Asian (81.4%) and <65 years of age (67.1%) (Table 2)

• The overall median age (range) was 60 years (32-78 years)

• Most patients had a baseline ECOG performance status of 1 (78.3%)

– 6 patients (3.7%) reported an ECOG performance status of 2

Table 2: Baseline characteristics

Demographic variable Phase 1bN=61

Phase 2N=100

Median age (range), years 58.0 (36-77) 61.0 (32-78)Sex, n (%)

FemaleMale

36 (59.0)25 (41.0)

52 (52.0)48 (48.0)

Race, n (%)AsianCaucasian

53 (86.9)8 (13.1)

78 (78.0)22 (22.0)

ECOG performance status, n (%)012

12 (19.7)45 (73.8)

4 (6.6)

17 (17.0)81 (81.0)

2 (2.0)ECOG, Eastern Cooperative Oncology Group

Overall survival• Median follow-up time (range) was 12.2 (0.9-70.2) months

• The overall median OS (95% CI) was 13.9 (11.6-15.7) months (Table 3)

Table 3: Overall survivalPhase 2N=100

No of events/N (%) 82/100 (82)Median overall survival (95% CI), months 13.9 (11.6 - 15.7)

% Event-free probability (95% CI)12 months24 months36 months48 months

58.4 (47.7 - 67.7)22.9 (14.7 - 32.2)12.1 (6.2 - 20.0)10.7 (5.2 - 18.4)

Figure 1: Kaplan-Meier plot of overall survival (Phase 2)

Prob

abili

ty o

f sur

viva

l

Time (months) 0100

484

866

1252

1633

2024

2419

2816

3211

3610

409

448

486

523

563

602

641

681

720All Patients

Number of patients at riskTime (months)

1.0

0.8

0.6

0.4

0.2

0.0

0

Censoring Times

Kaplan-Meier medians [95% CI] (months)All Patients: 13.93 [11.60; 15.67]

No of events/N = 82/100

4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72

Safety• Median duration of exposure (range):

– Phase 1b: 16 (0.4-209.7) weeks

– Phase 2: 18.5 (0.4-268.0) weeks

• 15 patients (9.3%) had died on-treatment

– The majority of deaths (10 patients, 6.2%) were attributed to the study indication, NSCLC

– Two patients (1.2%) died due to pneumonia and 1 patient each (0.6%) died due to dyspnea, myocardialinfarction and cerebrovascular accident

• Approximately one-third of patients had serious AEs (54 patients, 33.5%)

– The most frequent serious AEs (reported in ≥ 2.0% patients) were pneumonia, dyspnea (7 patients,4.3%), and pulmonary embolism (5 patients, 3.1%)

• Almost all patients (159 patients, 98.8%) experienced at least one AE; most being suspected to berelated to study treatment (140 patients, 87.0%)

• The most frequent AEs of any grade (reported in ≥25% of patients, regardless of causality) were nausea(36%), decreased appetite (32.9%), peripheral edema (32.3%), hypoalbuminemia (29.8%), vomiting(27.3%), and rash (25.5%)

Table 4: Treatment-related adverse events (reported in at least 10% of all patients)

Preferred term All patientsN=161

All grades n (%) Grade 3/4 n (%)

Total 140 (87.0) 51 (31.7)

Nausea 45 (28.0) 5 (3.1)

Peripheral oedema 37 (23.0) 8 (5.0)

Rash 35 (21.7) 2 (1.2)

Decreased appetite 34 (21.1) 3 (1.9)

Diarrhea 30 (18.6) 1 (0.6)

Paronychia 29 (18.0) 1 (0.6)

Vomiting 29 (18.0) 4 (2.5)

Increased amylase 25 (15.5) 10 (6.2)

Fatigue 23 (14.3) 4 (2.5)

Increased alanine aminotransferase 19 (11.8) 3 (1.9)

Lipase increased 18 (11.2) 10 (6.2)

Phase 1b/2 study of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated non-small cell lung cancer who received prior therapy: Final overall survival and safetyYi-Long Wu1, Li Zhang2, Dong-Wan Kim3, Xiaoqing Liu4, Dae Ho Lee5, James CH Yang6, Myung-Ju Ahn7, Johan F. Vansteenkiste8, Wu-Chou Su9, Enriqueta Felip10, Mariana Cabini11, Sabine Glaser11, Oezlem Tanriverdi11, Andrea Chassot Agostinho11, Daniel SW Tan12

1Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong, China; 2Sun Yat-sen University Cancer Center, Guangdong, China; 3Seoul National University Hospital, Seoul, Republic of Korea; 4Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing, China; 5University of Ulsan College of Medicine, Seoul, Republic of Korea; 6National Taiwan University Hospital, Taipei, Taiwan; 7Samsung Medical Center, Seoul, Republic of Korea; 8University Hospital KU Leuven, Leuven, Belgium; 9National Cheng Kung University Hospital, Tainan, Taiwan; 10Vall d’Hebron University Hospital, Barcelona, Spain; 11Novartis Pharma AG, Basel, Switzerland; 12National Cancer Centre Singapore, Singapore

Poster presented at the 2021 ASCO Annual Meeting, held virtually on 4–8 June 2021This study is sponsored by Novartis Pharma AG

Poster 9048

KEY FINDINGS AND CONCLUSIONS

Scan to obtain:• Poster

https://www.medicalcongress.novartisoncology.com/ASCO/Lung_Cancer/lung_cancer.html#WuYL90488409Copies of this poster obtained throughQuick Response (QR) code are for personal use onlyand may not be reproduced without permissionof the authors

INTRODUCTION• Capmatinib is a highly selective MET inhibitor approved for the treatment of adult patients with MET exon 14 skipping (METex14)-mutated,

advanced non-small cell lung cancer (NSCLC) based on results from the global phase 2 GEOMETRY mono-1 study (NCT02414139)1

• In the phase 1b/2 NCT01610336 study, we investigated the combination of capmatinib with an epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor (TKI), gefitinib in patients with EGFR-mutated and MET-dysregulated NSCLC who failed previous EGFR TKI therapy2

– The recommended phase 2 dose (RP2D) was capmatinib 400 mg twice-daily (bid) and gefitinib 250 mg once-daily (qd)– An objective response rate (ORR) of 29% was reported in phase 2, regardless of MET status in the primary analysis3

– The ORR was 47% in patients with high MET-amplified tumors (MET gene copy number ≥6)3,4

• Here, we report final overall survival (OS) and safety data from the study

RESULTS

Acknowledgements• We thank the patients, their families and caregivers, and the investigators who participated in the study• This study was sponsored by Novartis Pharmaceuticals Corporation• Medical writing and editorial assistance was provided by Aarti Kamaraj (Novartis Healthcare Pvt Ltd) and Varunkumar Pandey (Novartis Healthcare Pvt Ltd)

• Capmatinib 400 mg bid in combination with gefitinib 250 mg qd showed encouraging clinical activity in patients with EGFR-mutant and MET-dysregulated NSCLC– Median OS (95% CI) was 13.9 (11.6-15.7) months

• The combination was well tolerated• The most frequent AEs of any grade (reported in ≥25% of patients,

regardless of causality) were nausea (36%), decreased appetite (32.9%), peripheral edema (32.3%), hypoalbuminemia (29.8%), vomiting (27.3%), and rash (25.5%)

• The data suggests that combining MET inhibitor capmatinib with an EGFR-TKI may be a promising treatment option forEGFR-mutated, MET-dysregulated NSCLC, particularly for patients with MET amplified tumors

Presenting Author: Dr. Yi-Long Wusyylwu@live.cn

METHODS• This was an open-label, multicenter study, which

was composed of a phase 1b dose escalation partand a phase 2 dose expansion part

DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; FISH, Fluorescence In Situ Hybridization; IHC, Immunohistochemistry; MET, mesenchymal epithelial transition factor; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response evaluation criteria in solid tumors; RP2D, recommended phase 2 dose; TKI, tyrosine kinase inhibitor

Key eligibility criteria:• Locally advanced or metastatic NSCLC harboring

EGFR mutation (exon 19 deletion or L858R)• Clinical benefit with prior single-agent EGFR TKI

before progression• Dysregulated MET pathway post-progression on

EGFR TKIsa

• ECOG PS ≤2• ≥1 measurable lesion according to RECIST v1.1

(phase 2)

STUDY DESIGN2

Phase 1bcapmatinib + ge�tinib 250 mg

Phase 2capmatinib + ge�tinib 250 mg

Endpoints:

Primary: • ORR per RECIST v1.1

Secondary:• OS, DOR, PFS• Safety and tolerability• Pharmacokinetic profile

Initial expansion groupb in approximately 40 patientsDetermine

MTD or RP2D At least

18 patients MET dysregulation group in approximately 90 patients

aHigh MET expression was defined as ≥50% of tumor cells with IHC 3+, MET gene amplification was defined as gene copy number ≥4 by FISHbEnrollment of patients in the initial expansion group had stopped at the time when protocol Amendment 3 was approved by the Health Authority/Institutional Review Board at the study site.

References1. N Engl J Med 2020; 383: 944-9572. https://clinicaltrials.gov/ct2/show/NCT01610336 accessed on Apr 8, 20213. J Clin Oncol. 2018; 36(31): 3101-31094. J Clin Oncol. 2019; 37(3): 261

Disclosures (Dr Yi-Long Wu)Dr Yi-Long Wu reports personal fees from AstraZeneca (advisory board and speaker), Eli Lilly (speaker), Merck (advisory board and speaker), Pfizer (speaker), and Sanofi (speaker) outside the submitted work; grants and personal fees from Roche (advisory board and speaker) and Boehringer Ingelheim (advisory board and speaker) outside the submitted work

PHASE 1B/2 STUDY OF CAPMATINIB PLUS GEFITINIB IN PATIENTS WITH EGFR-MUTATED, MET-DYSREGULATED NON-SMALL CELL LUNG CANCER WHO RECEIVED PRIOR THERAPY: FINAL OVERALL SURVIVAL AND SAFETY

Dr Yi-Long Wu

Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong, China

Dr Yi-Long Wu

Introduction

• Capmatinib is a highly selective MET inhibitor approved for the treatment of adult patients with MET exon 14

skipping (METex14)-mutated, advanced non-small cell lung cancer (NSCLC) based on results from the global

phase 2 GEOMETRY mono-1 study (NCT02414139)1

• In the phase 1b/2 NCT01610336 study, we investigated the combination of capmatinib with an epidermal

growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib in patients with EGFR-mutated and

MET-dysregulated NSCLC who failed previous EGFR TKI therapy2

• The recommended phase 2 dose (RP2D) was capmatinib 400 mg twice-daily (bid) and gefitinib 250 mg once-daily (qd)

• An objective response rate (ORR) of 29% was reported in phase 2, regardless of MET status in the primary analysis3

• The ORR was 47% in patients with high MET-amplified tumors (MET gene copy number ≥6)3,4

• Here, we report final overall survival (OS) and safety data from the study

1. N Engl J Med 2020; 383:944-957

2. https://clinicaltrials.gov/ct2/show/NCT01610336 accessed on Apr 8, 2021

3. J Clin Oncol. 2018;36(31):3101-3109.

4. J Clin Oncol. 2019;37(3):261

Dr Yi-Long Wu

Methods

• This was an open-label, multicenter study, which was composed of a phase 1b dose escalation part and a

phase 2 dose expansion part

1. https://clinicaltrials.gov/ct2/show/NCT01610336 accessed on Apr 8, 2021

Key eligibility criteria:

• Locally advanced or metastatic

NSCLC harboring EGFR mutation

(exon 19 deletion or L858R)

• Clinical benefit with prior single-agent

EGFR TKI before progression

• Dysregulated MET pathway post-

progression on EGFR TKIsa

• ECOG PS ≤2

• ≥1 measurable lesion according to

RECIST v1.1 (phase 2)

Determine

MTD or

RP2D

At least 18

patients

Initial expansion groupb in

approximately 40 patients

MET dysregulation group in

approximately 90 patients

Phase 2

capmatinib + gefitinib 250 mgPhase 1b

capmatinib + gefitinib 250 mg

aHigh MET expression was defined as ≥50% of tumor cells with IHC 3+, MET gene amplification was defined as gene copy number ≥4 by FISHbEnrollment of patients in the initial expansion group had stopped at the time when protocol Amendment 3 was approved by the Health Authority/Institutional Review Board at the study site.

DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; FISH, Fluorescence In Situ Hybridization; IHC,

Immunohistochemistry; MET, mesenchymal epithelial transition factor; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival;

PFS, progression-free survival; RECIST, Response evaluation criteria in solid tumors; RP2D, recommended phase 2 dose; TKI, tyrosine kinase inhibitor

STUDY DESIGN1

Endpoints:

Primary:

• ORR per RECIST

v1.1

Secondary:

• OS, DOR, PFS

• Safety and tolerability

• Pharmacokinetic

profile

Results

Patient disposition• The study was completed on May 27, 2020

(last patient last visit), with 61 patients in

phase 1b and 100 patients in phase 2

• Out of the 161 patients who discontinued

from treatment phase, 130 patients (80.7%)

entered the survival follow-up and 31

patients (19.3%) discontinued from study

• Four patients alive at the end of the study

and 1 patient was transferred into a rollover

clinical study

• Most common reason for discontinuation of

study treatment was disease progression

(123 patients, 76.4%), followed by adverse

events (AEs, 19 patients, 11.8%)

Dr Yi-Long Wu

All patients

(N=161)

n (%)

Treatment phase

Completed 6 cycles of treatment

Discontinued from treatment phase

Entered survival follow-up

Discontinued from study

70 (43.5)

161 (100)

130 (80.7)

31 (19.3)

Primary reason for discontinuation from

treatment

Progressive disease

Adverse event

Subject/guardian decision

Death

Non-compliance with study treatment

Physician decision

Protocol deviation

Study terminated by sponsor

123 (76.4)

19 (11.8)

8 (5.0)

7 (4.3)

1 (0.6)

1 (0.6)

1 (0.6)

1 (0.6)

Results

Baseline characteristics• The majority of patients were Asian (81.4%)

and <65 years of age (67.1%)

• The overall median age (range) was 60

years (32-78 years)

• Most patients had a baseline ECOG

performance status of 1 (78.3%)

• 6 patients (3.7%) reported an ECOG

performance status of 2

Dr Yi-Long Wu

Demographic variablePhase 1b

N=61

Phase 2

N=100

Median age (range), years 58.0 (36-77) 61.0 (32-78)

Sex, n (%)

Female

Male

36 (59.0)

25 (41.0)

52 (52.0)

48 (48.0)

Race, n (%)

Asian

Caucasian

53 (86.9)

8 (13.1)

78 (78.0)

22 (22.0)

ECOG performance status, n

(%)

0

1

2

12 (19.7)

45 (73.8)

4 (6.6)

17 (17.0)

81 (81.0)

2 (2.0)

Results

Overall survival• Median follow-up time (range) was 12.2 (0.9-

70.2) months

• The overall median OS (95% CI) was 13.9

(11.6-15.7) months

Dr Yi-Long Wu

Phase 2

N=100

No of events/N (%) 82/100 (82)

Median overall survival (95% CI), months 13.9 (11.6 - 15.7)

% Event-free probability (95% CI)

12 months

24 months

36 months

48 months

58.4 (47.7 - 67.7)

22.9 (14.7 - 32.2)

12.1 (6.2 - 20.0)

10.7 (5.2 - 18.4)

Results

Kaplan-Meier plot of overall survival (Phase 2)

Dr Yi-Long Wu

Results

Safety

• Median duration of exposure (range):

• Phase 1b: 16 (0.4-209.7) weeks

• Phase 2: 18.5 (0.4-268.0) weeks

• 15 patients (9.3%) had died on-treatment

• The majority of deaths (10 patients, 6.2%) were attributed to the study indication, NSCLC

• Two patients (1.2%) died due to pneumonia and 1 patient each (0.6%) died due to dyspnea, myocardial infarction and

cerebrovascular accident.

• Approximately one-third of patients had serious AEs (54 patients, 33.5%).

• The most frequent serious AEs (reported in ≥ 2.0% patients) were pneumonia, dyspnea (7 patients, 4.3%), and pulmonary

embolism (5 patients, 3.1%).

Dr Yi-Long Wu

Results

Safety

• Almost all patients (159 patients, 98.8%)

experienced at least one AE; most being

suspected to be related to study treatment

(140 patients, 87.0%)

• The most frequent AEs of any grade

(reported in ≥25% of patients, regardless of

causality) were nausea (36%), decreased

appetite (32.9%), peripheral edema (32.3%),

hypoalbuminemia (29.8%), vomiting (27.3%),

and rash (25.5%)

Dr Yi-Long Wu

Preferred term

All patients

N=161

All grades n (%) Grade 3/4 n (%)

Total 140 (87.0) 51 (31.7)

Nausea 45 (28.0) 5 (3.1)

Peripheral oedema 37 (23.0) 8 (5.0)

Rash 35 (21.7) 2 (1.2)

Decreased appetite 34 (21.1) 3 (1.9)

Diarrhea 30 (18.6) 1 (0.6)

Paronychia 29 (18.0) 1 (0.6)

Vomiting 29 (18.0) 4 (2.5)

Amylase increased 25 (15.5) 10 (6.2)

Fatigue 23 (14.3) 4 (2.5)

Increased alanine aminotransferase 19 (11.8) 3 (1.9)

Lipase increased 18 (11.2) 10 (6.2)

Treatment-related adverse events (reported in at least 10% of all patients)

Key findings and conclusions

• Capmatinib 400 mg bid in combination with gefitinib 250 mg qd showed encouraging clinical activity in

patients with EGFR-mutant and MET-dysregulated NSCLC

• Median OS (95% CI) was 13.9 (11.6-15.7) months

• The combination was well tolerated

• The most frequent AEs of any grade (reported in ≥25% of patients, regardless of causality) were nausea

(36%), decreased appetite (32.9%), peripheral edema (32.3%), hypoalbuminemia (29.8%), vomiting (27.3%),

and rash (25.5%)

• The data suggests that combining MET inhibitor capmatinib with an EGFR-TKI may be a promising treatment

option for EGFR-mutated, MET-dysregulated NSCLC, particularly for patients with MET amplified tumors

Dr Yi-Long Wu