1093TiP - An open-label, multicenter, phase I/II clinical trial of RP1 as a single agent and in combination with nivolumab in patients with solid tumors [IGNYTE]

Background

RP1 is an enhanced potency oncolytic HSV-1 which expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). Pre-clinical studies with RP1 demonstrated potent GALV-GP R-enhanced anti-tumor activity and immunogenic cell death. This phase I/II (Ph I/II) study (NCT03767348) was designed to evaluate the safety and efficacy of RP1 as single agent and in combination with nivolumab (nivo) in pts with advanced solid tumors, including pts whose disease failed prior anti-PD1/PD-L1 therapy.

Trial design

This is a multi-center, first-in-human, open label, non-randomized Ph 1/2 study of RP1 alone and in combination with nivo in pts with advanced solid tumors, including those that failed prior anti-PD1/PD-L1 therapy. The Ph 1 dose escalation and expansion are fully enrolled. Approximately 260 pts are expected to be enrolled in the ongoing Ph 2 portion across five cohorts; melanoma (n=30, enrolment complete), non-melanoma skin cancer (n=45, to include 15 pts with anti-PD1/PD-L1 failed disease), MSI-H/dMMR (n=30), anti-PD1/PD-L1-failed non-small-cell lung cancer (n=30) and anti-PD1 failed cutaneous melanoma (n=125). Pts in the Ph 2 portion receive up to 10 mL of RP1 intratumorally into one or more deep/visceral and/or superficial lesions at the recommended Ph 2 dose (1x10⁶ PFU/mL × 1 followed by 1x10⁷ PFU/mL × 7). Following the first dose of RP1, nivo (240 mg IV Q2W for 4 months then 480 mg IV Q4W for up to 2 years) is subsequently administered in combination. Pts may receive up to 8 additional doses of RP1 if they meet protocol-specified criteria. Tumor assessments are performed Q8W. The primary objectives of the Ph 2 part of the study are to assess the safety, tolerability, and overall response rate (ORR) of RP1 in combination with nivo. Secondary objectives include duration of response, complete response rate, disease control rate, and PFS. Exploratory objectives include biodistribution and shedding analysis of RP1 and biomarker studies, including analyses of pre- and on-treatment tumor biopsies and blood samples. Enrollment is currently ongoing in the UK and US, with additional sites in the EU expected to open in 2021.

Clinical trial identification

NCT03767348.

Editorial acknowledgement

Legal entity responsible for the study

Replimune Group Inc.

Funding

Replimune Group Inc.

Disclosure

M.R. Middleton: Financial Interests, Personal and Institutional, Advisory Board: Alkermes Plc; Financial Interests, Personal, Advisory Board: Kineta Inc; Financial Interests, Personal, Advisory Board: Silicon Therapeutics; Financial Interests, Personal and Institutional, Advisory Board: Immunocore; Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board: Replimune Ltd; Financial Interests, Institutional, Sponsor/Funding: GlaxoSmithKline ; Financial Interests, Institutional, Sponsor/Funding: Merck KGaA; Financial Interests, Institutional, Sponsor/Funding: Merck & Co., Inc.; Financial Interests, Institutional, Sponsor/Funding: Pfizer Inc; Financial Interests, Institutional, Sponsor/Funding: Regeneron Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Bioline; Financial Interests, Institutional, Sponsor/Funding: Novartis International AG; Financial Interests, Institutional, Sponsor/Funding: F. Hoffmann-La Roche AG; Financial Interests, Institutional, Sponsor/Funding: Medivir; Financial Interests, Institutional, Sponsor/Funding: GenesisCare; Financial Interests, Institutional, Sponsor/Funding: GRAIL Inc. J.J. Sacco: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune ltd; Financial Interests, Personal and Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Personal and Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Sponsor/Funding: Immunocore; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Delcath. M.M. Milhem: Financial Interests, Personal, Advisory Role: Blueprints Medicine; Financial Interests, Personal, Advisory Role: Immunocore ; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Trieza; Financial Interests, Personal, Advisory Role: Array Biopharma; Financial Interests, Personal, Advisory Role: BioNTech SE; Financial Interests, Personal, Advisory Role: Novartis. A.M. VanderWalde: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune Group Inc; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Elsevier ; Financial Interests, Personal, Advisory Role: George Clinical; Financial Interests, Personal, Advisory Role: ConcertAI; Financial Interests, Personal, Advisory Role: Caris Life Sciences; Financial Interests, Personal, Advisory Role: ACCC; Financial Interests, Personal, Advisory Role: Mirati Therapeutics ; Financial Interests, Personal, Advisory Role: Genentech. J. Niu: Financial Interests, Personal, Principal Investigator: F. Hoffmann-La Roche AG; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Merck & Co., Inc; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: IMMVIRA; Financial Interests, Personal, Advisory Role: Johnson & Johnson; Financial Interests, Personal, Advisory Role: Takeda Pharmaceutical ; Financial Interests, Personal, Advisory Role: Exelixis, Inc; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Mirati Therapeutics. P.K. Bommareddy: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. L. Menezes: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. S. Samakoglu: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. A. Pirzkall: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. R.S. Coffin: Financial Interests, Personal, Stocks/Shares: Replimune Group Inc. K.J. Harrington: Financial Interests, Personal and Institutional, Sponsor/Funding: Replimune ltd; Financial Interests, Personal, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Sponsor/Funding: MSD; Financial Interests, Personal, Advisory Role: Arch Oncology; Financial Interests, Personal, Advisory Role: Oncolys BioPharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: PsiVac; Financial Interests, Personal, Advisory Role: Merck Serono. All other authors have declared no conflicts of interest.