1102P - Immune checkpoint inhibitor rechallenge after treatment with tumor-infiltrating lymphocytes in unresectable melanoma

Background

Adoptive cell therapy with tumor infiltrating lymphocytes (TIL) is a newly approved therapeutic strategy in melanoma refractory to immune checkpoint inhibitors (ICIs), but data to guide subsequent therapy decisions after TIL are limited. Specifically, the safety and efficacy of ICI rechallenge (often necessary due to limited alternatives) is unknown and may be affected by the infusion of large numbers of effector T cells with varying antigen specificity.

Methods

Patients with unresectable melanoma treated with sequential ICI therapy, TIL, and ICI rechallenge were identified at 10 international centers. Investigator-assessed response to ICI rechallenge was determined through radiographic and clinical review, and the response rate was calculated as the proportion of patients having a complete (CR) or partial (PR) response. Overall survival (OS) was calculated from post-TIL ICI treatment start to death or last follow up; duration of response (DOR) was calculated from date of response to progression, death, or last follow up.

Results

102 patients rechallenged with ICIs after melanoma progression on TIL therapy were identified. The most common M stage was M1c (59%) and LDH was elevated in 46% of patients; 80% of patients had received anti-PD-1 monotherapy prior to TIL and 50% had received prior nivolumab-ipilimumab (nivo-ipi). Toxicity and response data were available for 93 and 97 patients respectively. ICI-related toxicity was identified in 22 patients (24%), and among those 6 patients (27%) had a recurrence of a toxicity seen with pre-TIL ICI. Among 97 patients with available response data to ICI rechallenge, the response rate was 7.2% (2 CR; 5 PR; 95% CI 3.0-14%). Reponses were observed with nivo-ipi (n=5) nivolumab-relatlimab (n=1), and ipilimumab monotherapy (n=1); 6 of 7 responders were exposed to a new ICI after TIL. Median OS from ICI rechallenge was 7.7 months (95% CI 6.2-12 months); median DOR was not reached.

Conclusions

ICI rechallenge has limited clinical activity in patients with melanoma that has progressed following initial ICI treatment and TIL therapy, with most responses occurring after the introduction of a new agent. No unexpected safety signals were observed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Memorial Sloan Kettering Cancer Center; This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.

Disclosure

A. Betof Warner: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Novartis, Merck, Pfizer. J.W. Smithy: Financial Interests, Institutional, Coordinating PI: IO Biotech. R.N. Amaria: Financial Interests, Institutional, Coordinating PI: Merck, Bristol Myers Squibb, OnKure, Erasca, KSQ; Financial Interests, Institutional, Local PI: Roche; Financial Interests, Institutional, Trial Chair: Obsidian. M. Schollenberger: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb. A. furness: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Novartis, Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck, Bristol Myers Squibb, Novartis, Pierre Fabre, Immunocore; Financial Interests, Institutional, Research Grant: BMS Stiftung Immunokologie. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Sanofi, MSD, SunPharma, Amgen, GSK, Pierre Fabre, Immunocore, Delcath; Financial Interests, Institutional, Advisory Board: MSD, Novartis, BMS, Immunocore, Philogen, Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre, SunPharma, GSK, Onkowissen, Pierre Fabre; Financial Interests, Institutional, Writing Engagement: BMS; Financial Interests, Institutional, Research Grant: BMS, SunPharma, Sanofi; Financial Interests, Institutional, Local PI: Philogen, Genentech, 4SC, BioNTech, Iovance, Pierre Fabre, Regeneron, Sanofi, Replimune, Immatics, MSD, Pfizer, Agenus; Financial Interests, Institutional, Coordinating PI: BMS, Immunocore, Novartis, Genmab, Seagan; Financial Interests, Personal, Steering Committee Member: Immunocore, IO Biotech; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. M. Wermke: Financial Interests, Personal, Advisory Board: Novartis, Boehringer Ingelheim Ingelheim, Bayer, Bristol Myers Squibb, ImCheck Therapeutics, Immatics, Pfizer, AstraZeneca, Tacalyx GmbH, Regeneron, Zymeworks, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim-Ingelheim, Synlab GmbH, Janssen, EMD Merck Serono, GWT TUD GmbH, Amgen, Novartis; Financial Interests, Personal, Other, Member of DSMC: ISA Therapeutics; Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Other, Congress Travel Cost Support: AstraZeneca, EMD Merck Serono, Janssen, Boehringer Ingelheim Ingelheim, Immatics, Daiichi Sankyo, Iovance. J. Lutzky: Financial Interests, Personal, Other, reviewed grant applications for department of defense: general dynamics; Financial Interests, Personal, Advisory Board: regeneron, Immunocore; Financial Interests, Personal, Other, safety monitoring committee: Agenus, Celldex; Financial Interests, Institutional, Research Grant, Funding for institutional trial: BMS; Financial Interests, Institutional, Local PI: Trisalus, Takeda, Vyriad, Tango, Immunocore, Replimune, Oncohost, Dragonfly, Iovance, Ideaya. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Sanofi, Regeneron, Genentech, Eisai, Instil Bio, Natera, Nektar Therapeutics, Pfizer, Rain Therapeutics, CareDx, Immunocore, Novartis, Replimune, HUYA Bioscience International, Sun Pharma, Merck KGaA, Syneos; Financial Interests, Personal, Other, Consultant: OncoSec; Financial Interests, Personal, Stocks/Shares: Iovance; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb, Haystack Oncology; Financial Interests, Institutional, Local PI: Regeneron, Merck, Sanofi. R.J. Sullivan: Financial Interests, Personal, Advisory Board, Advisory board/consultancy: MSD; Financial Interests, Personal, Other, Consultant: Marengo; Financial Interests, Personal, Advisory Board, Consultancy/SAB: Novartis; Financial Interests, Personal, Other, Consultancy: Pfizer, Replimune; Financial Interests, Personal, Royalties: Up-to-Date; Financial Interests, Institutional, Coordinating PI, Phase I trial PI: Marengo; Financial Interests, Institutional, Local PI: Novartis, Synthekine, Immunocore, Springworks; Financial Interests, Institutional, Coordinating PI: Mural, Moderna; Financial Interests, Institutional, Steering Committee Member: Merck. H. Kluger: Financial Interests, Personal, Advisory Board, Consultatnt: Iovance; Financial Interests, Personal, Other, DSMC member: Celldex; Financial Interests, Personal, Advisory Board, Ad board participant: Array Biopharma, Calithera; Financial Interests, Personal, Advisory Board, Multiple advisory boards. Also have received institutional funds: Merck; Financial Interests, Personal, Advisory Board, Advisory boards and ALSO institutional funds: Bristol Myers Squibb; Financial Interests, Institutional, Other, Research funds: apexigen; Financial Interests, Personal, Advisory Board, Advisoary board participation: Clinigen; Financial Interests, Personal, Advisory Board, Advisory board: Shionogi; Financial Interests, Personal, Advisory Board, Ad board: Chemocentryx; Financial Interests, Personal, Advisory Board, Advisory board participant: Signatera; Financial Interests, Personal, Other, consultant: Gigagen; Financial Interests, Personal, Other, Response adjudication for a clinical trial: GI reviewers; Financial Interests, Personal, Advisory Board: Wherewolf; Financial Interests, Personal, Advisory Board, Ad board member: invox; Financial Interests, Institutional, Other, PI on investigator initiated trial funded partially by the company: Bristol Myers Squibb, Merck, Apexigen. K. Panageas: Financial Interests, Personal, Stocks/Shares: 23 and me. S. Klobuch: Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Local PI: Neogene. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Iovance Biotherapeutics, AstraZeneca; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Advisory Board: Third Rock Venture, CureVac, Imcyse; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio, Sastra Cell Therapy; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Other, Editor-in-Chief IOTECH: ESMO; Other, Other, Editorial Board ESMO Open: ESMO; Other, Other, Editorial Board: Kidney Cancer. A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore, Novartis, Erasca; Financial Interests, Personal, Royalties: UptoDate; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Immunocore, Pfizer, Novartis, Checkmate Pharmaceuticals, Linnaeus Therapeutics, Foghorn Therapeutics, Prelude Therapeutics, Iovance Biotherapeutics, Obsidian Therapeutics; Financial Interests, Institutional, Coordinating PI: Polaris, Xcovery, Targovax ASA; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.