Abstract 1094TiP
Background
Prognosis of advanced and metastatic cutaneous squamous cell carcinoma (CSCC) remains dismal. The anti-PD1 antibody cemiplimab was the first agent approved for the treatment of advanced CSCC. RP1 is an oncolytic virus (HSV-1) that expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, RP1 induced immunogenic tumor cell death and provided potent systemic anti-tumor activity. In preliminary study, high response rates including complete response have been observed in patients with CSCC treated with RP1 combined with nivolumab. The objective of this trial is to evaluate the safety and efficacy of RP1 + cemiplimab versus cemiplimab alone in advanced CSCC (NCT04050436).
Trial design
This global, multicenter, randomized phase II study is enrolling patients (pts) with metastatic CSCC or with unresectable, locally advanced CSCC who are not candidates for/refuse surgery or radiotherapy. Key eligibility criteria include no prior treatment with anti-PD1/PD-L1 antibodies or oncolytic viruses. The clinical trial will enroll approximately 180 pts at approximately 75 centers in the EU, Australia, Canada and USA. Pts will be randomized in a 2:1 ratio favoring the RP1 + cemiplimab arm. Pts will receive 350 mg of cemiplimab intravenously (IV) Q3W for up to 108 weeks. In the RP1 + cemiplimab arm, RP1 will be injected intratumorally at a starting RP1 dose of 1 × 106 plaque forming units (PFU)/mL alone, followed by up to 7 doses of RP1 at 1 × 107 PFU/mL Q3W together with cemiplimab. Pts in the combination arm may receive up to 8 additional RP1 doses. No crossover will be allowed. Pts will be stratified by disease status and prior systemic therapy. Tumor assessments will be performed every 9 weeks. Primary endpoints are overall response rate and complete response rate by blinded central review. Secondary endpoints include safety, progression free survival, duration of response and overall survival. Exploratory endpoints include viral shedding and biodistribution, and immune biomarker analyses. This trial is currently enrolling pts.
Clinical trial identification
NCT04050436.
Editorial acknowledgement
Legal entity responsible for the study
Replimune Group Inc.
Funding
Replimune Group Inc.
Disclosure
F. Collichio: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune Group Inc; Financial Interests, Personal and Institutional, Sponsor/Funding: Amgen; Financial Interests, Personal and Institutional, Sponsor/Funding: Novartis ; Financial Interests, Personal and Institutional, Sponsor/Funding: Merck & Co., Inc. A..D. Colevas: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune Group Inc. D. Rischin: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune Group Inc; Financial Interests, Personal and Institutional, Sponsor/Funding: Merck & Co., Inc; Financial Interests, Personal and Institutional, Sponsor/Funding: GlaxoSmithKline ; Financial Interests, Personal and Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Kura Oncology; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals. W. Chai-Ho: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune Group Inc. G. Daniels: Financial Interests, Institutional, Sponsor/Funding: Replimune Group Inc; Financial Interests, Personal, Invited Speaker: Clinigen; Financial Interests, Personal, Invited Speaker: St Joseph Health System ; Financial Interests, Personal, Invited Speaker: UME Education Inc . J. Lutzky: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune Group Inc; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb ; Financial Interests, Institutional, Sponsor/Funding: Vedanta Biosciences; Financial Interests, Institutional, Sponsor/Funding: Regeneron Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Foghorn Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Dragonfly Therapeutics ; Financial Interests, Institutional, Advisory Role: Sapience Therapeutics. J.H. Lee: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck & Co., Inc; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel Support : Bio-Rad Laboratories, Inc; Financial Interests, Personal, Other, Travel Support : Bio-Rad Laboratories, Inc; Financial Interests, Personal, Advisory Role: Sanofi. S. Bowyer: Financial Interests, Personal, Advisory Role: Sanofi S.A.. P. Sheladia: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. P.K. Bommareddy: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. S. He: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. C. Andreu-Vieyra: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. M.G. Fury: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals. All other authors have declared no conflicts of interest.