57O - Randomized Double-Blind Phase II Trial (PERLA) of Dostarlimab (dostar) + Chemotherapy (CT) vs Pembrolizumab (pembro) + CT in Metastatic Non-Squamous NSCLC: Primary Results

Background

PD-(L)1 inhibitors have a prominent role in the treatment (tx) of NSCLC, with pembro a commonly used agent, but with no direct comparisons between inhibitors to date. This global, randomized, Phase II double-blind study (PERLA; NCT04581824) compared the efficacy and safety of dostar + CT versus pembro + CT in patients (pts) with first-line (1L) metastatic non-squamous NSCLC.

Methods

Pts with no known EGFR, ALK or other genomic aberrations actionable locally by targeted therapies, known PD-L1 status, ECOG PS 0–1, and no prior systemic tx for metastatic NSCLC were randomized 1:1 to dostar 500 mg or pembro 200 mg Q3W IV ≤35 cycles, both in combination with CT (4 cycles pemetrexed [pem; 500 mg/m²] + carboplatin [AUC 5 mg/mL/min] or cisplatin [75 mg/m²] then pem up to cycle 35) Q3W IV. Primary endpoint was ORR by BICR (RECIST V1.1; difference by Mantel and Haenszel test and Sato’s variance estimator; point estimates by Clopper-Pearson). Safety was a secondary endpoint. Disease assessments were at wks 6 & 12, then every 9 wks x4, then every 12 wks.

Results

121 and 122 pts in the dostar + CT and pembro + CT arms were treated and evaluable, respectively; 41% and 42% had PD-L1 TPS <1; 36% had TPS 1–49% and 22% had TPS ≥50 in both arms. ORR was 46% for dostar + CT, with 2 complete responses [CRs] (2%) and 54 partial responses [PRs] (45%); ORR was 37% for pembro + CT, with 3 CRs (2%) and 42 PRs (34%) (9.3% difference [95% CI: −2.7–21.3]). Safety is shown in the table. Additional analyses (inc. PFS [secondary endpoint], PD-L1 sub-analyses and DOR [exploratory]) will be presented. Table: 57O

∗Permanent tx-discontinuation. TEAE, treatment-emergent adverse event

Conclusions

In this first randomized phase II study to directly compare PD-1 inhibitors, dostar + CT showed comparable efficacy to pembro + CT in 1L metastatic non-squamous non-oncogenic NSCLC. Safety profiles were similar and consistent with published data.

Clinical trial identification

NCT04581824.

Editorial acknowledgement

Dr. Peters and Dr. Lim are co-primary authors. Editorial support from Fishawack Health, 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, 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, Ro; 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. S.M. Lim: Financial Interests, Personal, Research Grant: Yuhan, Janssen; Financial Interests, Personal, Other, Consulting: AstraZeneca, Boehringer Ingelheim, Lilly, Takeda, J Ints Bio; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, GSK, Roche, Hengrui, BridgeBio Therapeutics, Oscotec, Daichii-Sankyo. 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. C.S. Fuentes: Financial Interests, Personal, Invited Speaker: Fundacion Respirar. G. Lo Russo: Financial Interests, Personal, Other, Consulting: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen , Sanofi, Italfarmaco, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi ; Financial Interests, Personal, Other, Travel: Roche, BMS, MSD ; Financial Interests, Personal, Advisory Role: Roche, Novartis, BMS, MSD, AstraZeneca, Sanofi ; Financial Interests, Personal, Other, PI in sponsored clinical trials: Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Sanofi . M. Schenker: Financial Interests, Personal and Institutional, Invited Speaker, Payment for Clinical trials activities: B.M.S., M.S.D., Roche, Merck Serono, Sanofi, Regeneron, AstraZeneca, Pfizer, G.S.K, Novartis, Astellas, Pharma Mar, BeiGene, Clovis Pharmaceutical, AbbVie, Bioven, Mylan, Samsung Pharmaceutical, Eisai, Gilead, Amgen, Daiichi Sankyo. J.S. Ahn: Financial Interests, Personal, Invited Speaker: Amgen Korea, Yuhan, AstraZeneca Korea, Menarini Korea, Bayer Korea, Takeda Phar, Novartis Korea, Hanmi, BC World, Pfizer, Roche Korea, Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Yuhan, Bayer Korea, Yooyoung, Pharmbio Korea, Vifor Pharma, Bixink. 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. N. Huseinovic: Financial Interests, Personal, Full or part-time Employment, Former employment: GSK; Financial Interests, Personal, Full or part-time Employment, Current employee: EQRx. E. Zografos: Financial Interests, Personal, Full or part-time Employment: GSK. S. O’Donnell: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Full or part-time Employment, Spouse is a US government employee: US Government. F. de Marinis: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Novartis, Merck, BMS, MSD. All other authors have declared no conflicts of interest.