LBA46 - Primary efficacy, safety, and survival data from the registration-intended cohort of patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial with RP1 combined with nivolumab

Background

Treatment options for patients (pts) with anti–PD-1–failed melanoma are limited and associated with high toxicity. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immunotherapy expressing GM-CSF and a fusogenic protein (GALV-GP-R−). The registration-intended cohort of the IGNYTE trial tested RP1 + nivolumab (nivo) in pts with advanced melanoma that progressed on anti–PD-1 therapy (NCT03767348).

Methods

Pts with confirmed progression (PD) while being treated with anti–PD-1 alone or combined with anti–CTLA-4 for ≥8 weeks as the last prior treatment, including as adjuvant, were enrolled. RP1 was given intratumorally at 1×10⁶ PFU/mL, then Q2W at 1×10⁷ PFU/mL up to 7x (≤10 mL/cycle) combined with nivo (240 mg IV), then nivo alone (240 mg Q2W or 480 mg Q4W IV) for up to 2 yrs, with further RP1 allowed if indicated. The protocol defined primary endpoint was ORR by independent central review (ICR) using modified RECIST (mRECIST 1.1), with assessment also by standard RECIST 1.1.

Results

Of 140 pts with advanced melanoma enrolled, 48.6% had stage IVb/c/d disease, 66.4% had primary anti–PD-1 resistance, 55.7% were PD-L1 negative, and 43.6% had prior anti–PD-1 + anti–CTLA-4. The confirmed ORR by ICR was 33.6% (15.0% CR) by mRECIST 1.1 and 32.9% by RECIST 1.1. Responses were in injected and non-injected, including visceral, lesions. The median (95% CI) response duration by mRECIST 1.1 was 21.6 (14.5–NR) months. The ORR was 34.4% in pts with primary anti–PD-1 resistance, and 26.2% in pts who received prior anti–PD-1 + anti–CTLA-4. Landmark OS rates (95% CI) at 1 and 2 years were 75.3% (66.9–81.9) and 63.3% (53.6–71.5); median OS was not reached. Most treatment-related adverse events (TRAEs) were grade 1–2; the grade ≥3 TRAE rate was 12.8%. There were no RP1-related deaths.

Conclusions

RP1 + nivo provided durable, clinically meaningful, antitumor activity with mostly grade 1–2 TRAEs in pts with advanced melanoma with confirmed PD while being treated with prior anti–PD-1 therapy alone or combined with anti–CTLA-4. Additional data will be presented.

Clinical trial identification

NCT03767348.

Editorial acknowledgement

Medical writing and editorial support were provided by Tony Sallese, PhD, of AlphaBioCom, a Red Nucleus company, and were funded by Replimune, Inc.

Legal entity responsible for the study

Replimune, Inc.

Funding

Replimune, Inc.

Disclosure

C. Robert: Financial Interests, Personal, Advisory Board, Consultancy fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, Pfizer, Sun Pharma, Merck, Ultimovacs, Regeneron, EGLE, Philogen, Maat Pharma; Financial Interests, Personal, Other, Steering Committee: Novartis, Regeneron, Pfizer, IO Biotech; Financial Interests, Personal, Other, IDMC: Ultimovacs; Financial Interests, Personal, Invited Speaker: Pierre Fabre, Sanofi, BMS, MSD, Novartis. M.M. Milhem: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Array, Biontech, Blueprints Medicine, Exicure, Immunocore, Novartis, Syneos, Trieza. J.J. Sacco: Financial Interests, Personal, Advisory Board, I have received honoraria for participation on advisory boards, both personal and to institution: Immunocore; Financial Interests, Institutional, Advisory Board: Immunocore, Replimune; Financial Interests, Personal, Advisory Board: Delcath; Financial Interests, Institutional, Local PI: Immunocore, Replimune, Qbiotics, MSD; Financial Interests, Institutional, Research Grant: Immunocore, AstraZeneca, BMS; Other, Travel and conference costs: MSD, Replimune. J. Michels: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK France; Financial Interests, Personal, Invited Speaker, Masterclass: Merck; Financial Interests, Personal, Other, Travel support: Merck; Financial Interests, Personal, Advisory Board: Brenus Pharma. G.K. In: Financial Interests, Institutional, Research Grant: Checkmate Pharma, InstilBio, Pfizer, Regeneron, Replimune, Inc., Xencor; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Array, BMS, Castle Biosciences, Regeneron, Replimune, Inc., Sanofi, Novartis. E. Muñoz-Couselo: Financial Interests, Personal, Advisory Board: BMS, Novartis, Sanofi, Pierre Fabre, Sun Pharma, MSD, Regeneron, Imunocore; Financial Interests, Personal, Invited Speaker: Novartis, Roche, BMS, Sanofi, MSD, Pierre Fabre; Non-Financial Interests, Member of Board of Directors, Vocal in the Society of Spanish Oncology group: SEOM; Non-Financial Interests, Member of Board of Directors, Member of the board directors in the Spanish Group of melanoma: GEM. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, MSD, Merck Serono, Sanofi, Neracare, SunPharma; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare, InFlarX, BioAlta, Daiichi Sanyko, NoviGenix, Anaveon, AstraZeneca, PamGene, BioNTech, Immatics, CureVac, Erasca, Formycon, Replimune, Seagen, SunPharma, Ultimovacs; Financial Interests, Personal, Steering Committee Member: Novartis, BMS, MSD; Financial Interests, Institutional, Coordinating PI: Novartis, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Institutional, Local PI: Sanofi, Philogen; Non-Financial Interests, Member of Board of Directors: EORTC-MG; Non-Financial Interests, Leadership Role, Founding member and SC chair: European Melanoma Registry (EuMelaReg). G.M. Beasley: Financial Interests, Personal, Invited Speaker, one day presentation of patient cases: BMS; Financial Interests, Institutional, Local PI: Philogen, Replimune, Delicate, Skyline. J.J. Niu: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, G1 Therapeutics, Mirati Therapeutics, Pfizer, Sanofi. B. Chmielowski: Financial Interests, Personal, Speaker, Consultant, Advisor: Delcath, Genentech, IDEAYA Biosciences, Instil Bio, Nektar, Novartis; Financial Interests, Institutional, Research Funding: Advenchen Laboratories, Bristol Myers Squibb, Compugen, Immunocore, Infinity Pharmaceuticals, Iovance, Karyopharm Therapeutics, Macrogenics, RAPT Therapeutics, Xencor, Ideaya Biosciences, Ascentage, Atreca, Replimune, Inc., InstilBio, Adagene, TriSalus Life Sciences, Kinnate, PTC Therapeutics; Financial Interests, Personal, Other, Travel support: InstilBio. T.M. Wise-draper: Financial Interests, Personal, Speaker, Consultant, Advisor: Caris Life Sciences, Exicure, Merck; Financial Interests, Personal, Other, Travel support: Caris Life Sciences; Financial Interests, Personal, Research Funding: AstraZeneca/MedImmune, Bristol Myers Squibb, Caris Life Sciences, GSK, Janssen Oncology, Merck; Financial Interests, Personal, Stocks or ownership: High Enroll. T.L. Bowles: Financial Interests, Institutional, Research Grant: Amgen, Genentech; Non-Financial Interests, Institutional, Other, Tumor testing: Natera. K.K. Tsai: Financial Interests, Institutional, Research Funding: ABM Therapeutics, BMS, Genentech, Oncosec, Pfizer, Regeneron, Replimune, Inc.; Financial Interests, Personal, Advisory Board: BMS, Regeneron. C. Lebbe: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre, Inflax; Financial Interests, Personal, Funding: Roche, Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Other, Honoraria, Speaker's Bureau, Research funding: Roche; Other, Honoraira, Speaker's bureau, Travel, Accommodations, Expenses, Research funding, Board: Bristol myers Squibb; Other, Honoraria, Speaker's bureau, Travel, Accommodations, Expenses, Board: Novartis, MSD; Other, Honoraria, Speaker's bureau: Amgen; Other, Honoraria, Travel, Accommodations, Expenses, Board: Pierre Fabre; Other, Honoraria,: Pfizer; Other, Honoraria: Incyte; Other, Travel, accommodations, Expenses, Board: Sanofi; Other, Board: Avantis Medical Systems, Jazz Pharmaceuticals; Other, Participation on a Data Safety Monitoring Board or Advisory Board: InflaRx. C. Gaudy Marqueste: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Pierre Fabre; Financial Interests, Institutional, Local PI: BMS, MSD, Pfizer, Amgen, GSK, Roche, Novartis, Pierre Fabre, Replimune, Jansen, Kartos, IFX, Huyabio, Regeneron, IO Biotech, Philogen, Sotio, Kinnate, AstraZeneca, Day One Biopharmaceuticals, Sairopa, Catalyst, Sanofi, Immunocore; Other, Travel expenses: BMS, Pierre Fabre, MSD. M.R. Middleton: Financial Interests, Personal, Speaker, Consultant, Advisor: Alkermes, Bayer, BiolineRx, Boehringer Ingelheim, Bristol Myers Squibb, Immunocore; Financial Interests, Institutional, Research Funding: Amgen, AstraZeneca, BiolineRx, Bristol Myers Squibb, Grail, Immunocore, Merck, Novartis, Regeneron, Replimune, Inc., Roche, SalvaRx, Vaccitech, Pfizer; Non-Financial Interests, Personal, Non financial benefits: GensisCare. A. Samson: Financial Interests, Institutional, Research Grant: Histosonics, Oncolytics, Stratosvir, Theolytics, Transgene; Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, Roche; Financial Interests, Personal, Invited Speaker: Roche. J. Zhu: Financial Interests, Personal, Full or part-time Employment: Replimune, Inc.; Financial Interests, Personal, Stocks/Shares: Replimune, Inc. M. Viana: Financial Interests, Personal, Full or part-time Employment: Replimune, Inc.; Financial Interests, Personal, Stocks/Shares: Replimune, Inc.; Financial Interests, Personal, Other, Travel support: Replimune, Inc.; Financial Interests, Personal, Advisory Board, Patent: Zentalis Pharmaceuticals. M.K.K. Wong: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Castle Biosciences, EMD-Serono, Exicure, Merck, Pfizer, Regeneron.