Efficacy of cemiplimab as monotherapy or in combination with chemotherapy in Japanese patients with advanced non-small cell lung cancer (aNSCLC)

BackgroundAnti-programmed death 1 inhibitors including cemiplimab have been shown to be effective in global populations for the treatment of aNSCLC. The multicentre phase 1/2 expansion study (NCT03233139) in treatment-naïve Japanese patients (pts) with aNSCLC assessed safety, tolerability, pharmacokinetics and efficacy of 1L cemiplimab as monotherapy or with chemotherapy.MethodsJapanese pts aged ≥20 years who had program death ligand 1 (PD-L1) expression ≥50% (Cohort A; n=60, safety; n=50, efficacy) received cemiplimab monotherapy, or any PD-L1 expression (Cohort C; n=50) received cemiplimab in combination with 4 cycles of chemotherapy. Cemiplimab was administered at 350 mg Q3W for up to 108 weeks. The primary analysis was performed when all pts had 3 post-baseline tumour assessments (∼28 weeks). Data cutoff was 5 Sep 2023 for Cohort A and 18 Oct 2023 for Cohort C.ResultsBaseline characteristics were similar across cohorts: median age was 65–70 years old and 76–80% were male. Median duration of follow up was 13.2 and 9.0 months in Cohorts A and C, respectively. In Cohort A, objective response rate (ORR) was 60% and median progression-free survival (PFS) was not reached (NR). Higher PD-L1 expression was associated with improvements in ORR and PFS. In Cohort C, ORR was 42% and median PFS was 8 months (Table). Median (95% CI) overall survival was 44.5 months (27.0–54.4) and NR (13.4–not evaluable) for Cohorts A and C, respectively. Immunogenicity was low in both cohorts. No new safety signals were identified in either cohort; adverse events ≥Grade 3 were experienced by 51.7% and 68.0% of pts in Cohorts A and C, respectively (Table).ConclusionsCemiplimab demonstrated consistent efficacy in Japanese pts as monotherapy for PD-L1 ≥50% and in combination with chemotherapy irrespective of PD-L1 expression. Safety was consistent with known safety profile of cemiplimab. Overall, cemiplimab demonstrated a favourable benefit-risk profile in Japanese pts. Table: 1384P Summary of results from cohorts A and C Cohort A (n=50) Cohort C (n=50) ORR Overall, n (%) 30/50 (60.0) 21/50 (42.0) 90% CI, % 48.6–71.4 30.5–53.5 PD-L1 ≥90%, n (%) 18/29 (62.1) – PD-L1 >60–<90%, n (%) 8/13 (61.5) PD-L1 ≥50–≤60%, n (%) 4/8 (50.0) – DOR KM median, months (95% CI) NR (19.2–NE) NR (6.6–NE) Range, months 2.1–42.5 2.3–20.7+ ≥6 months, n (%) 26/30 (86.7) 16/21 (76.2) PFS KM median, months (95% CI) NR (12.5–NE) 8.1 (6.0–NE) KM estimate at 24 months, % (95% CI) 51.9 (33.4–67.6) NE (NE–NE) Treatment-emergent adverse events, n (%)† Any 59 (98.3) 50 (100.0) ≥Grade 3 31 (51.7) 34 (68.0) Treatment discontinuation 22 (36.7) 19 (38.0) Death 0 2 (4.0) †n=60 (Cohort A)KM, Kaplan–Meier; NE, not evaluable. Clinical trial identificationNCT03233139.Editorial acknowledgementThe study was funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Editorial support was provided by Rachel McGrandle, MSc, of Alpha (a division of Prime, Knutsford, UK) funded by Regeneron Pharmaceuticals, Inc. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.Legal entity responsible for the studyRegeneron Pharmaceuticals, Inc.FundingRegeneron Pharmaceuticals, Inc.DisclosureY. Sato: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Novartis, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin. H. Ishii: Financial Interests, Personal, Other, Honoraria: AstraZeneca. S. Katakura: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Merck Sharp & Dohme, Eli Lilly, Takeda. M. Oki: Financial Interests, Personal, Research Funding: AbbVie Inc., Janssen Pharmaceutical K.K., MSD K.K., Parexel International Corporation, Sanofi K.K. T. Yokoyama: Financial Interests, Personal, Other, Honoraria: Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Research Funding: MSD, Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb Co. Ltd., Boehringer Ingelheim Japan Inc., Takeda Pharmaceutical Co., Ltd., Delta-Fly Pharma, Janssen Pharmaceutical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd. J. Pouliot, A.J. Paccaly, E. Kim, J. Mani, S. Li, I. Lowy, F. Seebach, M.D. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks or ownership: Regeneron Pharmaceuticals, Inc. S. Ikeda: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical Co. Ltd., Pfizer; Financial Interests, Personal, Research Funding: AstraZeneca, Chugai Pharmaceutical Co. Ltd. All other authors have declared no conflicts of interest.