Abstract 827P
Background
RP2 is an enhanced potency oncolytic herpes simplex virus (HSV) -1 expressing GM-CSF, a fusogenic protein (GALV-GP R-), and an anti-CTLA-4 antibody-like molecule that is being evaluated in an open-label, multicenter, phase 1 clinical trial as monotherapy and combined with nivolumab (nivo). Here, we present updated safety, efficacy, and biomarker data of RP2 ± nivo.
Methods
After determination of the RP2D (106 PFU/mL intratumorally (IT) once followed by up to 7 additional doses of 107 PFU/mL via IT), a cohort of 30 patients (pts) was enrolled and treated with RP2 combined with nivo (240 mg Q2W for 4 months from the second RP2 dose, then 480 mg Q4W for 20 months). Responses were assessed using modified RECIST v1.1.
Results
Objective responses with RP2 monotherapy were observed in 3 out of 9 pts including 1 CR for ≥15 months in mucoepidermoid carcinoma, 1 PR for ≥18 months in esophageal cancer with liver metastases, 1 PR in uveal melanoma with liver metastases that progressed at 15 months. Objective responses with RP2 + nivo treatment were 44.4% in cutaneous melanoma (4/9), 25% in uveal melanoma (2/8), and 33% in SCCHN (1/3) pts. All seven responding patients had previously failed anti-PD-1 therapy, with all but one response durable to date for >425 days. The most common adverse events (grade 1-2) were pyrexia, chills, influenza-like illness, fatigue, and pruritus. No grade 4-5 events were observed. Immunohistochemistry (IHC) analysis indicated robust increases in CD8 T cell influx, PD-L1 expression, and an increase in the CD8/foxp3+ cell ratio. Clinical responses were independent of baseline CD8 T cell infiltration, PD-L1 expression levels, and prior anti-PD-1 therapy status.
Conclusions
RP2 ± nivo demonstrated good tolerability and durable systemic responses in pts with difficult-to-treat, heavily pretreated and anti-PD-1 failed advanced cancers. These data continue to support the hypothesis that oncolytic delivery of anti-CTLA-4 into tumors, with accompanying antigen release, presentation and immune activation, can provide potent systemic anti-tumor effects.
Clinical trial identification
NCT04336241.
Editorial acknowledgement
Legal entity responsible for the study
Replimune Inc.
Funding
Replimune Inc.
Disclosure
K.J. Harrington: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Merck, MSD, Pfizer, Replimune, Oncolys, Vyriad, Idera; Financial Interests, Institutional, Other, Honoraria for lectures: Amgen, AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board, Advisory board for CD47 assets: Arch Oncology; Financial Interests, Institutional, Advisory Board, Development of DDR assets: ARTIOS; Financial Interests, Institutional, Advisory Board, Development of exosomal STING agonist: Codiak; Financial Interests, Institutional, Advisory Board, Development of oncolytic adenovirus: PsiVac; Financial Interests, Institutional, Funding, Research: AstraZeneca, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Funding, Development of oncolytic HSV platform: Replimune; Non-Financial Interests, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Other, Member of Global Steering Committee: MR - Linac. J.J. Sacco: Financial Interests, Institutional, Principal Investigator: Replimune Inc ; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, BMS, Immunocore; Financial Interests, Personal, Invited Speaker: Pierre- Fabre, BMS. P. Bommareddy: Financial Interests, Personal, Stocks/Shares: Replimune Inc . C. Ahlers: Financial Interests, Personal, Stocks/Shares: Replimune Inc . J. Wolff: Financial Interests, Personal, Stocks/Shares: Replimune Inc . M.R. Middleton: Financial Interests, Personal, Advisory Board, Advice on drug development and clinical trial design: Alkermes, Kineta, Silicon Therapeutics, Immunocore, Replimune; Financial Interests, Personal, Advisory Board, Advice on patient experience measures and research design: BMS; Financial Interests, Institutional, Invited Speaker, Fees for clinical trial conduct: Replimune; Financial Interests, Institutional, Invited Speaker, Fees for trial conduct: BMS, Alkermes, GSK, Merck KGa, MSD, Pfizer, Regeneron, Bioline, Novartis, Roche, Medivir; Financial Interests, Institutional, Funding, Educational grant towards IIS; fees for clinical trial conduct: Immunocore; Financial Interests, Institutional, Invited Speaker, Grant towards IIS: GRAIL; Non-Financial Interests, Other, Multiple roles as reviewer and committee member: Cancer Research UK; Non-Financial Interests, Member: AACR, ASCO, ACP. All other authors have declared no conflicts of interest.