Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies

Summary

Primary Objectives: * To characterize the safety and tolerability of isatuximab in combination with REGN2810 in participants with metastatic, castration-resistant prostate cancer (mCRPC) who were naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PD-L1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D). * To assess the response rate of isatuximab in combination with REGN2810 in participants with either mCRPC who were anti-PD-1/PD-L1 therapy naive, or NSCLC who progressed on anti-PD-1/PD-L1 therapy, or of isatuximab as single agent in participants with mCRPC. Secondary Objectives: * To evaluate the safety of the combination of isatuximab with REGN2810 or isatuximab monotherapy. * To evaluate the immunogenicity of isatuximab and REGN2810. * To characterize the pharmacokinetic (PK) profile of isatuximab single agent or in combination with REGN2810, and to characterize the PK of REGN2810 in combination with isatuximab. * To assess overall efficacy of isatuximab in combination with REGN2810 or as a single agent.

Timeline

Start

2018-01-04

Primary completion

2021-03-10

Completion

2021-03-10

Outcome

Missed primary endpoint

Stopped: “The study was stopped after interim analysis indicated that overall result was not sufficient to satisfy per-protocol criteria to move forward in metastatic, castration-resistant prostate cancer (mCRPC) and non-small cell lung cancer (NSCLC) cohorts.”

paper Per RECIST V.1.1, patients with NSCLC receiving Isa+Cemi achieved no CR or PR PMID 35058326 ↗

paper A lack of efficacy was observed in these small cohorts of patients with mCRPC or NSCLC. PMID 35058326 ↗

Publications

• Zucali PA, Lin CC, Carthon BC, Bauer TM, Tucci M, Italiano A, Iacovelli R, Su WC, Massard C, Saleh M, Daniele G, Greystoke A, Gutierrez M, Pant S, Shen YC, Perrino M, Meng R, Abbadessa G, Lee H, Dong Y, Chiron M, Wang R, Loumagne L, Lepine L, de Bono J. Targeting CD38 and PD-1 with isatuximab plus cemiplimab in patients with advanced solid malignancies: results from a phase I/II open-label, multicenter study. J Immunother Cancer. 2022 Jan;10(1):e003697. doi: 10.1136/jitc-2021-003697.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cemiplimab	Monoclonal antibody	—	Intravenous
Subject	Isatuximab	Monoclonal antibody	—	Intravenous

Indications