627MO - POD1UM-304: Phase III study of retifanlimab plus platinum-based chemotherapy (Chemo) as first-line (1L) therapy for nonsquamous or squamous metastatic non–small cell lung cancer (mNSCLC)

Background

Prognosis of advanced NSCLC disease remains poor. Checkpoint inhibitors (CPIs) including combinations with standard of care (SOC) chemo have shown survival benefit. POD1UM-304 evaluated the efficacy of retifanlimab, a PD-1 inhibitor, plus platinum-based chemo as 1L treatment (tx) for nonsquamous or squamous mNSCLC.

Methods

Patients (pts) aged ≥18 years with mNSCLC who have not received prior systemic tx for advanced disease, and do not harbor driver mutations or rearrangements of EGFR, ALK, BRAF, or ROS1 were enrolled. Pts were randomized 2:1 to retifanlimab 375 mg or matching placebo plus SOC platinum-based chemo for nonsquamous (pemetrexed + cisplatin/carboplatin q3w 4 cycles then pemetrexed q3w) or squamous (carboplatin + paclitaxel/nab-paclitaxel q3w 4 cycles) NSCLC for up to 2 years. The primary endpoint was overall survival; secondary endpoints were progression-free survival, overall response rate, duration of response, safety, and pharmacokinetics.

Results

A total of 583 (nonsquamous, 381; squamous, 202) pts were randomized (median [range] age 64.0 [29–84] years) and all study endpoints were met. Efficacy was improved with retifanlimab + chemo versus placebo + chemo (Table). Overall, higher incidences of serious and grade≥3 tx emergent adverse events (TEAEs) and TEAEs leading to tx interruptions or discontinuation were observed in the retifanlimab arm, consistent with the longer exposure to tx in this group versus the placebo arm. Notably, no increase in fatal or serious COVID-19–related TEAEs were observed with the addition of retifanlimab Table: 627MO

Efficacy by blinded independent central review of retifanlimab + platinum-based chemo versus placebo + platinum-based chemo in 1L mNSCLC

Conclusions

Retifanlimab improved overall survival when added to platinum-based chemo and the safety profile of the combination was consistent with other CPIs. Adding retifanlimab to SOC 1L chemo could be a tx option for mNSCLC.

Clinical trial identification

NCT04205812.

Editorial acknowledgement

Medical writing assistance was provided by Upasna Thapar, PhD, of Envision Pharma Group (Fairfield, CT, USA).

Legal entity responsible for the study

Incyte Corporation, Wilmington, DE, USA.

Funding

Incyte Corporation, Wilmington, DE, USA.

Disclosure

S. Lu: Financial Interests, Institutional, Research Funding: AstraZeneca, Hutchison, Heng Rui, Beigene, Roche, Hansoh; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co. Ltd.; Financial Interests, Personal, Advisory Board: Simcere Zaiming Pharmaceutical Co. Ltd., Shanghai Fosun Pharmaceutical, Phanes Therapeutics, Inc; Financial Interests, Personal, Member of Board of Directors: Innovent Biologics, Inc. Y. Kulyaba: Financial Interests, Personal, Research Funding: AstraZeneca. A. Ibrahim: Financial Interests, Personal, Other, Speaker honorarium: AstraZeneca, Mundipharma, Boehringer Ingelheim, Novartis, GSK, Menarini, Orient Europharma; Financial Interests, Personal, Other, Clinical Advisory: Boehringer Ingelheim, Novartis. F.V. Moiseenko: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Takeda, Sanofi, Pfizer, Biocad, Novartis, MSD, Merck, Lilly, Boehringer Ingelheim, BMS, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, AstraZeneca, Novartis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Takeda, Lilly, Boehringer Ingelheim, BMS, Roche; Financial Interests, Institutional, Research Funding: BIOCAD; Financial Interests, Personal, Other, Travel, accommodations,: Boehringer Ingelheim, Pfizer, Takeda; Financial Interests, Personal, Other: educational activities provided by Pfizer, AstraZeneca, MSD, BMS, Roche. C. Arslan: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Novartis, BMS, Merck Sharp & Dohme, AstraZeneca, Johnson & Johnson, Lilly, Amgen, Astellas, Teva, Pfizer, Bayer; Financial Interests, Personal, Research Funding: Roche, Novartis, BMS, Merck Sharp & Dohme, AstraZeneca, Nektar, Johnson & Johnson, Lilly, Amgen, Astellas, Amgen, Teva, Bayer, Henlius, Yuhan, Daiichi Sankyo, Pfizer, Sanofi-Aventis, AstraZeneca, Nektar, Johnson & Johnson, Lilly, Amgen, Astellas, Teva, Bayer, Henlius, Yuhan, Daiichi Sankyo, Pfizer, Sanofi-Aventis. I. Cicin: Financial Interests, Institutional, Speaker, Consultant, Advisor: Pfizer, MSD Oncology (Inst), Roche (Inst), Novartis/Ipsen (Inst), Eli Lilly (Inst), Bristol Myers Squibb (Inst), Servier (Inst), Abdi Ibrahim (Inst), Nobelpharma (Inst), AbbVie (Inst), Teva, Janssen Oncology (Inst); Speakers' Bureau - Novartis (Inst), Roche (Inst, Roche, Novartis/Ipsen, Eli Lilly, Bristol Myers Squibb, Servier, Abdi Ibrahim, Nobelpharma, AbbVie, Teva, Janssen Oncology; Financial Interests, Institutional, Speaker’s Bureau: Novartis, Roche, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Abdi Ibrahim. M. Cornfeld, C. Tian, M. Munteanu: Financial Interests, Personal, Full or part-time Employment: Incyte Corporation; Financial Interests, Personal, Stocks/Shares: Incyte Corporation. All other authors have declared no conflicts of interest.