Abstract 17P
Background
PERLA (NCT04581824) is the first trial to compare two programmed cell death protein-1 (PD-1) inhibitors, dostarlimab vs pembrolizumab, in combination with chemotherapy (DCT and PCT, respectively). Previous analyses showed numerical improvements in progression-free survival (PFS), overall response rate, and overall survival (OS) for DCT versus PCT (Lim et al, Nat Commun, 2023; Peters et al, presented at SITC 2024). Here we report the final PFS, OS, and safety analyses for PERLA.
Methods
Patients with confirmed metastatic non-small cell lung cancer (NSCLC), documented PD-ligand (L) 1 status, ECOG Performance Status Scale 0–1, no actionable genomic aberrations, and no prior systemic treatment were randomized 1:1 to a combination of 4 cycles of CT Q3W IV (pemetrexed [500 mg/m2] + carboplatin [AUC 5 mg/mL/min] or cisplatin [75 mg/m2], followed by pemetrexed up to 35 cycles [up to 24 months]), combined with either 500 mg dostarlimab or 200 mg pembrolizumab, Q3W IV up to 35 cycles (24 months). PFS and OS were assessed by Kaplan-Meier (KM) method and 95% confidence intervals (CIs) were calculated by Brookmeyer-Crowley method; hazard ratios (HRs) were estimated by Cox proportional hazard model stratified by PD-L1 status and smoking status at randomization. Duration of follow-up was assessed using reverse KM method.
Results
As of last patient last visit (Sep 10, 2024), the median duration of follow-up for OS was 35.5 months for DCT and 35.2 months for PCT. Median OS (months, 95% CI) was 20.2 (14.5–27.3) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.55–1.02] at 70% maturity). Median PFS (months, 95% CI) was 8.8 (6.9–11.0) for DCT and 6.8 (4.9–7.1) for PCT (HR 0.77 [95% CI: 0.58–1.03] at 79% maturity). Safety profiles were consistent with previous analyses. Profiles and outcomes of patients who completed 35 cycles or 2 years of treatment will be described.
Conclusions
The final PERLA analysis has consistently demonstrated strong clinical efficacy, including durable OS, and safety of DCT as a first-line treatment for patients with metastatic non-squamous NSCLC comparable to PCT. Funding: GSK (213403).
Clinical trial identification
NCT04581824.
Editorial acknowledgement
Editorial support was provided by Nakeirah Christie, PhD, Claire Kelly, PhD, and Elizabeth Ohneck, PhD, of Fishawack Indicia Ltd., part of Avalere Health, and was funded by GSK.
Legal entity responsible for the study
GSK.
Funding
GSK (213403).
Disclosure
S. Peters: Financial Interests, Personal, Advisory Role: 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, Personal, Research Grant: Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, Merck Sharp and Dohm, Roche/Genentech. A.L.O. Ortega Granados: Financial Interests, Personal, Full or part-time Employment: Servicio Andaluz de Salud; Financial Interests, Personal, Advisory Role: Roche, Bristol Myers Squibb, Merck Sharp and Dohme. C.S. Fuentes: Financial Interests, Personal, Invited Speaker: Fundacion Respirar. G. Lo Russo: Financial Interests, Personal, Other, Consulting: Roche, Novartis, BMS, MSD, Pfizer; Financial Interests, Personal, Officer, Consulting: AstraZeneca, Takeda, Amgen, Sanofi, Italfarmaco; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi; Financial Interests, Personal, Other, Travel grant: Roche, BMS, MSD; Financial Interests, Personal, Advisory Role: Roche, Novartis, BMS, MSD, AstraZeneca, Sanofi; Financial Interests, Personal, Sponsor/Funding, Investigator on sponsored clinical trial: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Sanofi. M. Schenker: Financial Interests, Personal, Principal Investigator, Contract for clinical trial activities (institutional and personal as site Principal Investigator): GSK, Merck Serono, BMS, MSD, Roche, Sanofi, Regeneron, Astellas, Amgen, Bayer, BeiGene, Clovis, Tesaro, Gilead, Bioven, Novartis, Pfizer, Eli Lilly, Pharma Mar, AbbVie, AstraZeneca, Mylan, Daiichi Sankyo. J.S. Ahn: Financial Interests, Personal, Invited Speaker: Kyowa Kirin, Amgen Korea, Yuhan, AstraZeneca Korea, Menarini Korea, Bayer Korea, Takeda Pharmaceutical, Novartis Korea, Hanmi, BCWorld, Pfizer, Roche Korea, Boehringer Ingelheim, Vifor Pharma, Bixink; Financial Interests, Personal, Advisory Role: Yuhan, Bayer Korea, Yooyoung, Pharmbio Korea. F. de Marinis: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Novartis, Merck, BMS, MSD. K.J. Locke: Financial Interests, Personal, Full or part-time Employment: GSK. 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; Financial Interests, Personal, Stocks/Shares: GSK. I. Diaz-Padilla: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks/Shares: GSK. S.M. Lim: Financial Interests, Personal, Research Grant: Yuhan, Janssen, AstraZeneca, BeiGene, Boehringer Ingelheim, GSK, Roche, Hengrui, BridgeBio Therapeutics, Oscotec, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting: AstraZeneca, Boehringer Ingelheim, Lilly, Takeda, Guardant, J Ints Bio. All other authors have declared no conflicts of interest.