Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Abstract

Background: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).

Methods: The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.

Results: For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan-Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).

Conclusion: In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.

Trial registration number: Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://ichgcp.net/clinical-trials-registry/NCT02760498.

Keywords: immunotherapy; programmed cell death 1 receptor; tumor biomarkers.

Conflict of interest statement

Competing interests: DR: institutional research grant and funding from Regeneron Pharmaceuticals, Inc., Sanofi, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, and GlaxoSmithKline; uncompensated scientific committee and advisory board from Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, and Bristol-Myers Squibb; travel and accommodation from Merck Sharp & Dohme and GlaxoSmithKline. MRM: honoraria and travel expenses from Regeneron Pharmaceuticals, Inc., Sanofi, Novartis, Genentech, Eli Lilly, and Sun Pharma; and institutional research funding from Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Eli Lilly. AML: uncompensated advisory board from Merck Sharp & Dohme and Bristol-Myers Squibb with travel and accommodation expenses. CDS: steering committee member for Castle Biosciences; a steering committee member and consultant for Regeneron Pharmaceuticals, Inc.; a consultant for Sanofi; has received research funding from Castle Biosciences, Regeneron Pharmaceuticals, Inc., Novartis, Genentech, and Merck, and is a chair for the National Comprehensive Cancer Network. NIK: grants from Regeneron Pharmaceuticals, Inc.; grants and advisory board fees from Bristol-Myers Squibb and HUYA Bioscience International; advisory board fees from EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, Array BioPharma, and Immunocore; grants from Merck, Novartis, GlaxoSmithKline, Celgene, and Amgen; honorarium from Sanofi; and common stock ownership of Bellicum Pharmaceuticals, Mazor Robotics, Amarin, and TransEnterix. BGMH: consulting or advisory roles at Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Pfizer, Roche, Eisai, Merck, and institutional research funding from Amgen. DS: institutional patients’ fees from Regeneron Pharmaceuticals, Inc.; advisory board honorarium fees from Amgen and Leo Pharma; speaker fee from Boehringer Ingelheim; advisory board, speaker honorarium and patients’ fees from Roche, Novartis, Bristol-Myers Squibb, and Merck-EMD; advisory board and speaker honorarium fees from Incyte and Pierre Fabre; advisory board honorarium and patients’ fees from Merck Sharp & Dohme, steering committee honorarium fees from 4SC, advisory board fees from AstraZeneca, Pfizer, and Array; and advisory board and patients’ fees from Philiogen. LAD: advisory role at Regeneron Pharmaceuticals, Inc., and research funding from Eisai, Pfizer, Regeneron Pharmaceuticals, Inc. LH-A: performed consulting and advisory roles at Massive Bio; speakers’ bureau roles at Sanofi and Regeneron Pharmaceuticals, Inc., and received travel, accommodations, and expenses from Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol-Myers Squibb, and research funding from Bristol-Myers Squibb, Regeneron Pharmaceuticals, Inc., Immunocore, Merck Sharp & Dohme, Polynoma, Corvus Pharmaceuticals, Roche, Merck Serono, Amgen, MedImmune, and Takeda. ALSC: consulting and advisory roles at Regeneron Pharmaceuticals, Inc., Merck; research funding from Regeneron Pharmaceuticals, Inc., Novartis, Galderma, and Merck. BM: speaker’s honoraria, travel, accommodations and expenses from Regeneron Pharmaceuticals, Inc. and Sanofi. AH: institutional grants, speaker’s honoraria, and consultancy fees from Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche, and Novartis; institutional grants and consultancy fees from Merck Serono, Philogen, and Regeneron Pharmaceuticals, Inc.; and consultancy fees from OncoSec. CU: honoraria, consulting, or advisory roles, speaker’s bureau role, research funding and travel, accommodation, and expenses from Novartis, Sanofi, Galderma, and Almirall. TE: consulting or advisory roles at Sanofi Genzyme, Bristol-Myers Squibb, Roche, Novartis and Merck Sharp & Dohme; speakers’ bureau role at Roche and Merck Sharp & Dohme and research funding from Novartis and Bristol-Myers Squibb. BS: consulting or advisory roles at Merck Sharp & Dohme and Merck KGaA Australia. ACP: honoraria and consulting or advisory roles at Bristol-Myers Squibb, Merck, Regeneron Pharmaceuticals, Inc., Array, Novartis, Seattle Genetics, Amgen; research funding from Bristol-Myers Squibb, Merck, Regeneron Pharmaceuticals, Inc., Celldex, and Forance and travel, accommodation, expenses from Regeneron Pharmaceuticals, Inc., Array, and Seattle Genetics. JLG: research institution support for the study from and advisory board for Regeneron Pharmaceuticals, Inc. RG: honoraria from Almirall Hermal GmbH, Amgen, AstraZeneca, Bristol-Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Regeneron Pharmaceuticals, Inc., Roche/Genentech, Sanofi, and Sun Pharma; consulting or advisory role for 4SC, Almirall Hermal GmbH, Amgen, Bristol-Myers Squibb, Incyte, LEO Pharma, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche/Genentech, Sun Pharma, and Takeda; research funding from Amgen, Johnson & Johnson, Novartis, and Pfizer; travel, accommodations, expenses from Bristol-Myers Squibb, Merck Sorono, Pierre Fabre, and Roche. MA: consulting or advisory roles for Pulse Biosciences and Revance Therapeutics. EO, MM, VJ, ES, JB, SL, IL, MGF: employees and shareholders of Regeneron Pharmaceuticals, Inc. AG: personal fees and non-financial support (advisory board and travel support) from Bristol-Myers Squibb and Sun Pharma; personal fees (advisory board) from Merck KGaA, Eisai, and Pfizer; non-financial (travel) support from Astellas; and clinical trial unit support from PPD Australia.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Best tumor response per RECIST 1.1 by independent central review for (a) Group 3 and (b) Group 1. This figure shows best percent change in the sum of tumor diameters for patients who had at least one post-baseline radiologic assessment (39 of 56 patients in Group 3 and 45 of 59 patients in Group 1). Lesion measurements after progression were excluded and patients who did not have at least one post-treatment radiologic assessment of target lesion(s) are not shown. The dashed lines indicate RECIST 1.1 criteria for partial response (≥30% decrease in sum of diameters) or progression (≥20% increase in sum of diameters) of target lesions. Patients with new lesions or unequivocal progression of non-target lesions are considered as progressive disease (red bars) regardless of target lesion response. Patients with a single assessment with ≥30% reduction of target lesion(s) are considered stable disease (blue bars) if there is not confirmatory assessment to establish partial response. One patient in Group 1 was not evaluable (NE) (yellow bar); this patient had radiologic and photographic data and was, therefore, reviewed by Independent Composite Review Committee and assessed as NE. Patients who did not have at least one evaluable post-baseline radiology assessment are not included in the figure but are included in the overall response analysis (table 2) per intention-to-treat. Increase in sum of target lesion diameters greater than 100% is reported as 100%. RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1.