327P - Three years survival outcome and continued cemiplimab (CEMI) beyond progression with the addition of chemotherapy (chemo) for patients (pts) with advanced non-small cell lung cancer (NSCLC): The EMPOWER-lung 1 trial

Background

In the EMPOWER-Lung 1 trial, CEMI monotherapy provided a significantly improved overall survival (OS) and an acceptable safety profile vs chemo in pts with newly diagnosed advanced NSCLC. We are reporting the 3-year survival data of the trial. Also, we are presenting the first efficacy data of pts who continued CEMI at progression (PD) with the addition of histology-specific chemo.

Methods

Pts were randomized 1:1 to CEMI 350 mg IV every 3 weeks for 2 years or investigator’s choice of chemo. Pts randomized to CEMI with PD, confirmed by a blinded independent review committee (BIRC), were allowed to continue CEMI with the addition of up to 4 cycles of chemo. To be included in the post PD analysis, pts had to receive at least one dose of chemo and have at least one scan following PD on CEMI. Response to continued CEMI + chemo was assessed by BIRC against a new baseline, defined as the last scan prior to the initial dose of chemo.

Results

At median follow-up of 37.1 months (m; range: 24.0 : 56.5), median OS (mOS) was 23.4 m (19.4, 27.4) for CEMI pts (N=357) vs 13.7 m (11.2, 16.2) for chemo pts (N=355), with hazard ratio (HR) of 0.634 (0.524, 0.768); median progression free survival (mPFS) was 6.3 m (4.6, 8.3) vs 5.3 m (4.3, 6.0), HR 0.560 (0.470, 0.666). 64 pts continued CEMI + chemo as 2L therapy. Continued CEMI + chemo as 2L therapy resulted in a 31.3% objective response rate and a mOS of 15.1 m (11.3, 18.7), and was generally tolerated, with 19 pts (29.7%) experiencing serious treatment-emergent adverse event (TEAE), and 3 pts each with TEAE resulting in discontinuation of study treatment or death.

Conclusions

At 3 year follow-up, HRs of CEMI vs. chemo improved (vs at 13 m follow-up) for both PFS and OS despite 76% crossover rate, an exceptional finding in the NSCLC field. Continued CEMI + chemo as 2L therapy provided meaningful and durable ORR and OS benefits and these results compare favorably to historical data of pts receiving chemo alone as 2L therapy (after immune-checkpoint inhibitor monotherapy). This data is the first report from a Phase 3 study providing therapeutic advantage to pts who progress after 1L PD1 monotherapy.

Clinical trial identification

NCT03088540.

Editorial acknowledgement

Medical writing support was provided by Osnat Ben-Shahar PhD from Regeneron, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc., and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosure

M. Özgüroğlu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals Inc., Sanofi. M. Schenker: Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Astellas, AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono, Merck Sharpe & Dohme, Novartis, Pfizer, Regeneron, Roche. I. Cicin: Financial Interests, Personal, Advisory Role: AbbVie, Abdi Ibrahim, Bristol Myers Squibb, Janssen Oncology, Lilly, MSD Oncology, Nobelpharma, Novartis/Ipsen, Pfizer, Roche, Servier, Teva; Financial Interests, Personal, Speaker’s Bureau: Abdi Ibrahim, Bristol Myers Squibb, Novartis, Pfizer, Roche. G.F. Ho: Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Merck & Co., Inc., Novartis, Roche, Boehringer Ingelheim; Financial Interests, Personal, Other, Chairperson: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: EliLily, Regeneron, Merck & Co., Inc., AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer; Non-Financial Interests, Institutional, Product Samples: Pfizer, Eli Lilly, Novartis, Janssen Pharmaceuticals. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. J. Pouliot: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. All other authors have declared no conflicts of interest.