Presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, 19–21 September, 2020

Abbreviations1L, first line; AE, adverse event; ALK, anaplastic lymphoma kinase; CI, confidence interval; CR, complete response; DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; EOT, end of treatment; HRD, homologous recombination deficiency; IV, intravenously; mITT, modified intent-to-treat; NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PARPi, poly (ADP-ribose) polymerase inhibitor; PD-1, programmed cell death receptor 1; PD-1i, programmed cell death receptor 1 inhibitor; PD-L1, programmed cell death ligand 1; PD-(L)1i, programmed cell death receptor 1 or programmed cell death ligand 1 inhibitor; PFS, progression-free survival; PR, partial response; Q3W, every 3 weeks; Q9W, every 9 weeks; Q12W, every 12 weeks; RECIST, response evaluation criteria in solid tumours; ROS1, c-ros oncogene 1; TEAE, treatment-emergent adverse event; TPS, tumour proportion score.

DisclosuresSSR reports non-financial and other support from GSK; grant funding and other support (for consultancy) from Amgen, BMS, Merck, GSK, AstraZeneca and Takeda; grant funding from Tesaro and Advaxix; other support (for consultancy) from AbbVie and Genentech/Roche. ET and NIS declare no conflicts of interest. MMA reports grant funding and personal fees from Genentech, BMS, AstraZeneca; personal fees from Merck, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar and Gritstone; grant funding from Lilly. AD reports other and non-financial support from GSK; grant funding (to the institution) from EMD Serono, Tesaro, Roche, Vertex, Regeneron, Eli Lilly, Takeda, Ipsen, United Therapeutics, Mirati, BMS, Incuron and Bayer; grant funding (to the institution) and personal fees (for consultancy) from AbbVie, AstraZeneca, Millenium, and Seattle Genetics; personal fees (for consultancy) from Ariad. BH reports other and non-financial support from GSK. TS reports other and non-financial support from GSK; personal fees (for advisory boards) from Takeda, AstraZeneca, Genentech/Roche, G1 Therapeutics, Foundation Medicine, EMD Serono, Novartis and Lilly Oncology; grant funding (to the institution) from Genentech/Roche, Blueprint Medicines, Merck, AstraZeneca, Takeda, Advaxis and Regeneron. GKD reports other, personal fees (for consultancy) and non-financial support from GSK. DRS reports grant funding (to the institution) and a consulting/advisory role for GSK, Genentech/Roche, Novartis, Celgene, BMS, AstraZeneca, Lilly, Merck, Nektar, Takeda and EMD Serono; a consulting/advisory role (with funds to the institution) for Pfizer, Boehringer Ingelheim, AbbVie, Foundation Medicine, Moderna Therapeutics, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeutics, Illumina, PharmaMar, Aptitude Health, Bayer, Dracen Pharmaceuticals, Iksuda Therapeutics, Molecular Templates, Seattle Genetics, Intellisphere and TRIPTYCH Health Partners; grant funding (to the institution) from University of Texas Southwestern Medical Center - Simmons Cancer Center, G1 Therapeutics, Neon Therapeutics, Celldex, Clovis Oncology, Daiichi Sankyo, Astellas Pharma, GRAIL, Transgene, Aeglea Biotherapeutics, Tesaro, Ipsen, Janssen, MedImmune, BIND Therapeutics, Eisai and ImClone Systems. LE and IT are employees of and hold stocks/shares in GSK. NIS, ZW, YT and MR are employees of GSK.

AcknowledgementsEditorial assistance was provided by Emily Mercadante and Katie Pfaff at Fishawack Indicia Ltd, UK, and funded by GSK. This study was funded by GSK study 213352; NCT03308942. The authors would like to thank Andrea Lee Veatch and Subramanya Rao for their contributions to this work. The authors would like to acknowledge Hasan Jamal, publications manager, for his contributions to this publication.

References1. WHO Cancer Key Facts 2018.2. NIH SEER Cancer Stat Facts 2020.3. Low JL, et al. Ther Adv Med Oncol 2019;11:1–22.4. Keytruda Prescribing information 2020.5. Paz-Ares L, et al. N Engl J Med 2018;379:2040–51.6. Nowicki TS. Cancer J 2018;24:47–53.7. Nosaki K, et al. Lung Cancer 2019;135:188–95.8. Jiao S, et al. Clin Cancer Res 2017;23:3711–20.9. Vinayak S. JAMA Oncol 2019;5:1132–40.10. Niraparib US Prescribing Information. April 2020. 11. Niraparib Summary of Product Characteristics. January 2020.12. Sandhu S, et al. Lancet Oncol 2013;14:882–92.13. Konstantinopoulos PA, et al. JAMA Oncol 2019;5:1141–9.14. Mok TSK, et al. Lancet 2019;393:1819–30.15. Mirza MR, et al. N Engl J Med 2016;375:2154–64.16. Moore KN, et al. Lancet Oncol 2019;20:636–48.

Suresh S. Ramalingam1, Eddie Thara2, Mark M. Awad3, Afshin Dowlati4, Basir Haque5, Thomas Stinchcombe6, Grace K. Dy7, David R. Spigel8, Nithya Iyer Singh9, Lena Evilevitch9, Zhaojie Wang9, Yongqiang Tang9, Iryna Teslenko9, Mahua Roychoudhury9

1Emory University, Winship Cancer Institute, Atlanta, GA, USA; 2The Oncology Institute of Hope & Innovation, Los Angeles, CA, USA; 3Dana-Farber Cancer Institute, Boston, MA, USA; 4University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH, USA; 5Kadlec Clinic Hematology & Oncology, Kennewick, WA, USA; 6Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA; 7Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; 8Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA; 9GSK, Waltham, MA, USA

JASPER: Efficacy and Safety of First-Line (1L) Niraparib Plus a Programmed Death Receptor 1 Inhibitor (PD-1i) in Patients With Advanced Non–Small Cell Lung Cancer (NSCLC)Poster number: 1268P | Presenting author: Suresh S. Ramalingam ssramal@emory.edu

Background Methods (Continued) Safety

Conclusions

Efficacy

Treatment period†

Cycle 1

Screening*

Day 1 Day 8

Safety assessments: Day 1, 8, 15 of Cycle 1; Day 1 of all subsequent cyclesTumour assessments: 9w after first dose; Q9W until Week 72; Q12W thereafter

Day 15 Day 21EOT period‡

Safety assessments:30 + 7d after EOT;

follow-up assessmentevery 90 ± 14d

Tumour assessments§:Q9W until week 72;

Q12W thereafter

All patientsreceivedniraparib 200 mgPO QD and pembrolizumab200 mg IV Q3W

Efficacy Analysis:mITT population: Received any study drugand did not withdraw consent prior to having≥1 post-baseline tumour assessment¶

Safety Analysis:Received ≥1 dose ofthe study treatment

Statistical Analysis: Sample size was calculated for eachcohort based on primary endpointof ORR; SAS software, version 9.4

Patie

nts

Duration on treatment (months)–1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Cohort 1 (PD-L1 TPS: ≥50%)*

2 CRs were reported ORR† 56% (9/16 patients)(95% CI: 30–80)

Complete responsePartial responseStable diseaseProgressive diseaseOngoingEnd of combination treatment

End of monotherapyEnd of TreatmentEnd of StudyDeathNiraparib + PembrolizumabNiraparibPembrolizumab

Patie

nts

Duration on treatment (months)–1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Cohort 2 (PD-L1 TPS: 1–49%)‡

ORR† 20% (4/20 patients)(95% CI: 6–44)

Complete responsePartial responseStable diseaseProgressive diseaseOngoingEnd of combination treatment

End of monotherapyEnd of TreatmentEnd of StudyDeathNiraparib + PembrolizumabNiraparibPembrolizumab

Perc

ent c

hang

e

Patients

20% incr

30% decr

In Cohort 1, patients had 8–100% reduction in target lesion size

Patients

150

130

110

90

70

50

30

10

–10

–30

–50

–70

–90

–110

SD

SD SD

SD PR PR SD PR PR PRPR PR

CRCR

Perc

ent c

hang

e

2 patients died in Cohort 1 and 3 patients in Cohort 2 prior to tumour assessment scan

20% incr

30% decr

In Cohort 2, patients had 9–78% reduction in target lesion size150

130

110

90

70

50

30

10

–10

–30

–50

–70

–90

–110

PD PD

SD SD PD SD

PD SD SDSD SD

SD PR

PRPR PR

SD

PD-L1 TPS: 1–49%

PD-L1 TPS: ≥50%

Lung cancer is the most commonly diagnosed cancer globally, yet outcomes are poor in advanced cancer, representing an unmet need1,2

The PD-1 signalling axis has emerged as a therapeutic target in patients with advanced NSCLC3

• Pembrolizumab is a PD-1i approved as 1L single-agent therapy for patients with advanced NSCLC with PD-L1 TPS ≥1%4,5

The benefit of PD-(L)1 therapies is limited to a subset of patients with NSCLC6

Furthermore, patients who cannot tolerate 1L chemotherapy, such as elderly patients, may benefit from additional therapeutic options7

The combination of PARPi with PD-1i may enhance antitumour activity of immune checkpoint inhibitors alone8,9

Primary endpoint:ORR, Investigator-

assessed per RECIST v1.1

Secondaryendpoints:

DoR, PFS, OS, Safety

Cohort 1(niraparib +

pembrolizumab)PD-L1

TPS ≥50%

Cohort 2(niraparib +

pembrolizumab)PD-L1

TPS 1–49%

Metastatic or locally advanced NSCLC• ≥18 years of age• Chemotherapy-naïve• PD-(L)1 inhibitor-naïve• Measurable disease

per RECIST v1.1• Stage IIIB or

Stage IV NSCLC• No known EGFR-

sensitising mutations, ALKor ROS1 translocations

• ECOG PS 0–1• PD-L1 expression

(TPS) available

patientsreceived

niraparib andpembrolizumab

NN 38

The study was conducted in the USA beginning September 2017 and is ongoing

Cohort 1 (PD-L1 TPS ≥50%)

Cohort 2 (PD-L1 TPS 1–49%)

Number of patients

17 21Median age

72 years 72 years

Female

6 (35%) 12 (57%)

ECOG PS

29.4% ECOG 0

58.8% ECOG 1

11.8% ECOG 2*

28.6% ECOG 0

71.4% ECOG 1

Histology at diagnosis

64.7% Adenocarcinoma

29.4% Squamous cell

5.9% Other

66.7% Adenocarcinoma

23.8% Squamous cell

9.5% Other

Tumour stage

5.9% Stage IIIB/ unresectable

94.1% Stage 4†

100% Stage 4†

*Two patients had ECOG PS 1 at screening, and worsened to ECOG PS 2 on C1D1 which was documented as the baseline ECOG PS. Inclusion criteria were verified based on screening ECOG PS and patients were deemed eligible; †recurrent or metastatic.

Niraparib is a selective PARP1/2i, given orally10,11

Niraparib is approved as first- and second-line maintenance treatment for advanced or recurrent fallopian tube, epithelial ovarian and primary peritoneal cancer in patients with CR or PR to platinum-based chemotherapy, respectively, and for the treatment of patients with advanced HRD-positive ovarian, fallopian tube or primary peritoneal cancer after ≥3 chemotherapy regimens10,11

Niraparib monotherapy showed preliminary antitumour activity in 2 patients with NSCLC in a Phase 1 trial12

The combination of niraparib and pembrolizumab was evaluated in the Phase 2 TOPACIO trial in patients with triple-negative breast cancer and platinum-resistant ovarian cancer, where it demonstrated a tolerable safety profile and promising antitumour activity9,13

JASPER (NCT03308942) is a proof-of-concept Phase 2 study of the combination of niraparib and PD-1i in chemotherapy-naïve and PD-(L)1i-naïve patients with metastatic or locally advanced NSCLC

ObjectiveTo report interim data on the efficacy and safety of the combination of niraparib and pembrolizumab in patients with PD-L1 TPS ≥50% (Cohort 1) and PD-L1 TPS 1–49% (Cohort 2)

OS data were immature at the time of analysis

Methods

Results

TEAEs in >2 patients in either cohort, n (%)

Cohort 1PD-L1 TPS ≥50%

(N=17)

Cohort 2PD-L1 TPS 1–49%

(N=21)Any TEAE 17 (100) 21 (100)

Any TEAE related to either study drug 15 (88.2) 18 (85.7)

Fatigue 7 (41.2) 7 (33.3)

Nausea 6 (35.3) 9 (42.9)

Decreased appetite 5 (29.4) 8 (38.1)

Anaemia 4 (23.5) 7 (33.3)

Constipation 4 (23.5) 2 (9.5)

Platelet count decreased 2 (11.8) 5 (23.8)

Vomiting 2 (11.8) 4 (19.0)

Dyspnoea 2 (11.8) 3 (14.3)

Any niraparib-related TEAE 15 (88.2) 16 (76.2)

Any pembrolizumab-related TEAE 14 (82.4) 15 (71.4)

Any Grade ≥3 TEAE 15 (88.2) 18 (85.7)

Anaemia 4 (23.5) 6 (28.6)

Pneumonia 4 (23.5) 4 (19.0)

Fatigue 2 (11.8) 3 (14.3)

Dyspnoea 1 (5.9) 5 (23.8)

Platelet count decreased 1 (5.9) 3 (14.3)

Neutrophil count decreased 0 3 (14.3)Any Grade ≥3 TEAE related to either study drug 11 (64.7) 13 (61.9)

Anaemia 4 (23.5) 3 (14.3)

Platelet count decreased 1 (5.9) 3 (14.3)

Any Grade ≥3 niraparib-related TEAE 10 (58.8) 11 (52.4)Any Grade ≥3 pembrolizumab- related TEAE 7 (41.2) 7 (33.3)

Any serious TEAE 11 (64.7) 14 (66.7)Any serious TEAE related to either study drug 6 (35.3) 5 (23.8)

Deaths due to AEs 1 (5.9) 3 (14.3)

Discontinued niraparib due to TEAE 10 (58.8) 8 (38.1)

Discontinued pembrolizumab due to TEAE 4 (23.5) 5 (23.8)

Median DoR and PFS were higher in Cohort 1 compared with Cohort 2

Cohort 1(PD-L1 TPS ≥50%)

Cohort 2(PD-L1 TPS 1–49%)

Median DoR,* months (95% CI) 19.7 (4.2–NE)n=9

9.4 (4.2–15.1)n=4

Median PFS,† months (95% CI) 8.4 (3.9–22.1)n=16

4.2 (2.0–6.2)n=20

*Median DoR assessed in mITT population among patients with CR/PR; †median PFS assessed in mITT population.

Niraparib, a PARPi, in combination with pembrolizumab, a PD-1i, induced durable responses in patients with advanced or metastatic NSCLC in both study cohorts• Greater efficacy was observed in Cohort 1 patients with PD-L1–high tumours

(PD-L1 TPS ≥50%)The safety profile of the combination was consistent with prior clinical experience with niraparib and pembrolizumab, as monotherapy or in combination, in other tumour types9,14-16

• While the number of patients is relatively small, these results suggest that niraparib plus a PD-1i is an active and well-tolerated combination and support further evaluation of this novel combination approach in advanced NSCLC

2Phase 2

Open-label

Multiarm

Multicentre

*Includes initial safety monitoring and baseline tumour assessment; scans performed as part of routine clinical management are acceptable for use as initial tumour imaging if they are of diagnostic quality and performed within 28 days prior to first dose date;†until discontinuation due to death, progressive disease, unacceptable toxicity, severe noncompliance with the protocol, withdrawal of consent, pregnancy, confirmed CR in patient who has >24w of treatment and 2 cycles after CR confirmed, or study termination; ‡until death or end of study data collection (minimum 6 months after enrolment of the last patient); §if patient discontinues treatment for a reason other than progression, death, withdrawal of consent, or loss to follow-up; ¶mITT population included treated patients who died prior to the first scan.

The data cut-off date for this analysis was February 7, 2020

Clinical responses were reported in both cohorts

*Cohort 1 enrolled 17 patients; 1 patient withdrew consent prior to the first dose; mITT n=16; †mITT population; confirmed ORR includes patients with CR and PR. mITT includes all patients who received any study drug and did not withdraw consent prior to having at least one post-baseline tumour assessment; ‡Cohort 2 enrolled 21 patients; 1 patient withdrew consent prior to the first dose; mITT n=20.

Please find the online version of this poster by scanning the quick response (QR) code or via http://tqr.bz/u4c.

Copies of this e-poster obtained through QR code are for personal use only and may not be reproduced

without written permission of the authors.

Please send questions to Suresh Ramalingam ssramal@emory.edu or Iryna Teslenko iryna.x.teslenko@gsk.com

?

Baseline demographics, disease characteristics