First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies
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Abstract
Purpose: This first-in-human study assessed the safety, tolerability, dose-limiting toxicities (DLT), antitumor activity, and pharmacokinetics of cemiplimab, a monoclonal anti-programmed cell death-1 (PD-1), as monotherapy and in combination with hypofractionated radiotherapy (hfRT) and/or cyclophosphamide (CPA) in patients with advanced solid tumors. Patients and Methods: Patients were enrolled in 1 of 10 dose escalation cohorts and received cemiplimab 1, 3, or 10 mg/kg every 2 weeks intravenously for up to 48 weeks. Depending on the cohort, patients received hfRT and/or low-dose (200 mg/m2) CPA. Safety was evaluated. Antitumor activity was assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Results: Sixty patients were enrolled. The median duration of follow-up was 19.3 weeks (range, 2.3–84.3). There were no DLTs. The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (45.0%), nausea (36.7%), and vomiting (25.0%). The most common immune-related adverse events (irAEs) of any grade were arthralgia (10.0%), hypothyroidism (8.3%), and maculopapular rash (8.3%). Cemiplimab pharmacokinetic parameters increased in a close to dose-proportional manner and were similar regardless of combination therapy regimen. Two patients (one with cutaneous squamous cell carcinoma and one with cervical cancer) experienced a complete response; 7 had a partial response. Observed duration of response was ≥12 months in 6 patients. Conclusions: The safety profile of cemiplimab was comparable with other anti–PD-1 agents. Addition of hfRT and/or CPA did not appear to increase grade ≥3 irAEs, suggesting that cemiplimab can be safely administered with hfRT and/or CPA. Cemiplimab exhibited encouraging antitumor activity with 2 complete responses and 7 partial responses observed; responses were also durable.
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α-PD-1/PD-L1 plus chemoradiotherapy was tolerable in advanced NSCLC, HNSCC, and SCLC patients, with promising clinical outcomes, in phase 1/2 studies.
“Moreover, the results of some phase 1/2 studies (NCT02621398, NCT02434081, NCT02586207, NCT02383212, and NCT02402920) showed that α-PD-1/PD-L1 plus chemoradiotherapy was tolerable in advanced NSCLC, head and neck squamous cell carcinoma (HNSCC), and SCLC patients, with promising clinical outcomes [78–82].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [81]
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Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
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- Authors
- Papadopoulos, K. P., Johnson, M. L., Lockhart, A. C., Moore, K., Falchook, G. S., Formenti, S. C., Naing, A., Carvajal, R. D., Rosen, L. S., Weiss, G. J., Leidner, R. S., Li, J., Paccaly, A., Feng, M., Stankevich, E., Lowy, I., Fury, M. G., & Crittenden, M. R.
- Affiliations
- South Texas Accelerated Research Therapeutics (US)
- Sarah Cannon (US)
- Washington University in St. Louis (US)
- OU Health Stephenson Cancer Center (US)
- HealthONE (US)
- Weill Cornell Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- Columbia University Irving Medical Center (US)
- University of California, Los Angeles (US)
- Western Regional Medical Center (US)
- Providence Portland Medical Center (US)
- 12Regeneron Pharmaceuticals, Inc., Basking Ridge, New Jersey.
- Regeneron (United States) (US)
- Oregon Clinic (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2020-03-01
- Volume
- 26
- Issue
- 5
- Pages
- 1025-1033
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2993204321
- Cited by
- 66
- References
- 13
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 18 · 2021: 15 · 2020: 7
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Regeneron Pharmaceuticals, Inc. (N/A)
- Sanofi (N/A)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- cemiplimab, PD-1 inhibitors, hypofractionated radiotherapy, cyclophosphamide, immune checkpoint inhibitor combination, advanced solid tumors, immune-related adverse events, anticancer activity, pharmacokinetics, dose-limiting toxicity, first-in-human safety
- MeSH terms
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Cyclophosphamide, Dose-Response Relationship, Drug, Fatigue, Female, Humans, Male, Middle Aged, Nausea, Neoplasm Staging, Neoplasms, Treatment Outcome, Chemoradiotherapy, Antibodies, Monoclonal, Humanized, Patient Safety, Response Evaluation Criteria in Solid Tumors
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