LBA64 - Overall survival from a phase II randomised double-blind trial (PERLA) of dostarlimab (dostar) + chemotherapy (CT) vs pembrolizumab (pembro) + CT in metastatic non-squamous NSCLC

Background

The Phase II PERLA trial (NCT04581824) was the first global randomized, double-blind, head-to-head study of two programmed death (PD)-1 inhibitors in NSCLC. In the primary analysis, dostar + CT met its primary endpoint of equivalence, with a favorable numerical trend in overall response rate (ORR) and progression-free survival compared to pembro + CT [1]. Here we report overall survival (OS) analyses from PERLA.

Methods

Patients (pts) with metastatic NSCLC, documented PD-L1 status, absence of EGFR, ALK or other actionable genomic aberrations determined locally, ECOG 0–1, and no prior systemic treatment were randomised 1:1 to dostar 500 mg or pembro 200 mg Q3W IV up to 35 cycles, combined with CT (4 cycles pemetrexed [pem; 500 mg/m²] + carboplatin [AUC 5 mg/mL/min] or cisplatin [75 mg/m²], followed by pem up to 35 cycles) Q3W IV. The primary endpoint was ORR by blinded independent central review (BICR). OS (secondary endpoint) and duration of response (DoR) by BICR (exploratory endpoint) were determined by Kaplan-Meier method, 95% confidence intervals (CIs) by Brookmeyer-Crowley method and hazard ratio by stratified Cox proportional hazard model.

Results

At data cut-off on 07 July 2023, 121 and 122 pts in the dostar + CT and pembro + CT arms respectively, were randomised and treated. OS maturity was 55% (134/243). Median OS was 19.4 mo (95% CI 14.5, NR) in the dostar + CT arm vs 15.9 mo (95% CI 11.6, 19.3) in the pembro + CT arm (Table), after median follow-up (IQR) of 20.7 (17.3, 24.0) and 21.6 (18.3, 24.1) mo respectively, with a similar trend across PD-L1 subgroups. ORR and DoR are shown in the table. No new safety signals were reported. Table: LBA64

*Brookmeyer-Crowley method; ^†based on profile-likelihood confidence limits; ^‡according to RECIST v1.1; ^§Clopper-Pearson method; ^¶Mantel and Haenszel method with Sato variance estimator. CI, confidence interval; CR, complete response; mo, months; NR, not reached; PR, partial response.

Conclusions

In this follow-up analysis, dostar + CT continues to demonstrate strong clinical efficacy with no unexpected safety signals. In addition, a numerical trend in OS favoring dostar + CT vs pembro + CT was observed. 1. Peters, S et al. IOTECH 2022;16(S1):100162 Funding:GSK (213403).

Clinical trial identification

NCT04581824.

Editorial acknowledgement

Editorial support was provided by Claire Kelly, PhD, and Mary-Clare Cathcart, PhD, of Fishawack Indicia Ltd., part of Fishawack Health, and was funded by GSK.

Legal entity responsible for the study

GSK.

Funding

GSK.

Disclosure

S. Peters: Financial Interests, Personal, Advisory Board: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Peerview, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody; Financial Interests, Personal, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Beigene, Bristol Myers Squibb, GSK, Merck Sharp and Dohme, Roche/Genentech. A.L.O. Ortega Granados: Financial Interests, Personal and Institutional, Full or part-time Employment: Servicio Andaluz de Salud; Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme. F. de Marinis: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Novartis, Merck, BMS, MSD. G. Lo Russo: Financial Interests, Personal, Other, Consulting: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi, Italfarmaco, Pfizer, GSK; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi, GSK; Financial Interests, Personal, Other, Travel: Roche, BMS, MSD; Financial Interests, Personal, Advisory Role: Roche, Novartis, BMS, MSD, AstraZeneca, Sanofi, GSK; Financial Interests, Personal, Other, Principle Investigator in sponsored clinical trials: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Sanofi. M. Schenker: Financial Interests, Personal and Institutional, Other, Clinical trial activities: GSK, BMS, MSD, Roche, AstraZeneca, Merck Serono, Astellas, Amgen, Bayer, Beigene, Clovis, Gilead, Eli Lilly, Pfizer, Novartis, Sanofi, Pharma Mar, AbbVie, Regeneron, Mylan, Samsung Pharmaceuticals, Bioven, Eisai, Five Prime, Daiichi Sankyo. E. Arriola: Financial Interests, Personal, Advisory Role: BMS, Roche, MSD, Pfizer, Lilly, AstraZeneca, Boehringer Ingelheim, Takeda ; Financial Interests, Personal, Invited Speaker: BMS, Roche, MSD, Pfizer, Lilly, AstraZeneca, Boehringer Ingelheim, Takeda ; Financial Interests, Personal and Institutional, Research Grant: Roche, Pfizer; Financial Interests, Institutional, Funding: BMS, Roche, Pfizer; Financial Interests, Personal, Ownership Interest: Trialing Health. J.M. Puig: Non-Financial Interests, Personal, Principal Investigator: CER San Juan, Centro Polivalente de Asistencia e Investigación Clinica. D.H. Lee: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CJ Healthcare, Eli Lilly, ChongKeunDang, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, ST Cube, AbbVie, Takeda, Menarini, BC Pharma, Yuhan ; Non-Financial Interests, Personal, Other, Non-financial: Takeda, Blueprint Medicine. M. Reck: Financial Interests, Personal, Advisory Role, Lectures and consultancy: Amgen, AstraZeneca, BeiGene, BMS, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, Merck, MSD, Novartis, Pfizer, Regeneron, Roche, Samsung Bioepsis, Sanofi. Z. Szijgyarto: Financial Interests, Personal, Full or part-time Employment: GSK. E. Buss: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks/Shares: GSK. N. Stjepanovic: Financial Interests, Personal, Full or part-time Employment: GSK. S.M. Lim: Financial Interests, Personal, Research Grant: Yuhan, Janssen, Roche; Financial Interests, Personal, Other, Consulting: AstraZeneca, Boehringer Ingelheim, Lilly, Takeda, J Ints Bio; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, GSK, Hengrui, BridgeBio Therapeutics, Oscotec, Daiichi-Sankyo.