First-In-Human Study of Cemiplimab Alone or in Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies

Kyriakos P. Papadopoulos, Melissa L. Johnson, Albert C. Lockhart, Kathleen Moore, Gerald S. Falchook, Silvia C. Formenti, Aung Naing, Richard D. Carvajal, Lee S. Rosen, Glen J. Weiss, Rom S. Leidner, Jingjin Li, Anne Paccaly, Minjie Feng, Elizabeth Stankevich, Israel Lowy, Matthew G. Fury, Marka R. Crittenden

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1025-1033
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number5
DOIs
StatePublished - Mar 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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. (2020). First-In-Human Study of Cemiplimab Alone or in Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. Clinical Cancer Research, 26(5), 1025-1033. https://doi.org/10.1158/1078-0432.CCR-19-2609