Abstract 844P
Background
Lifileucel showed durable responses in patients (pts) with advanced (unresectable/metastatic) melanoma in the post anti–PD-1 setting, with an ORR of 36% (Sarnaik JCO 2021). The recent approval of relatlimab (anti–LAG3 antibody) + nivolumab provides a new option for first-line (1L) treatment of advanced melanoma; however, ORR after exposure to this novel combination has been reported only for anti–CTLA-4–based therapies (11%; Menzies NEJM 2022).
Methods
In the phase 2, C-144-01 study (NCT02360579), pts with advanced melanoma were previously treated with immune checkpoint inhibitor(s) (ICI) and BRAF ± MEK inhibitors (if BRAF V600 mutation-positive). We performed a retrospective exploratory analysis to assess efficacy and safety of lifileucel in pts enrolled in C-144-01 who progressed on/after anti-LAG3–containing therapy. ORR was assessed by investigators per RECIST v1.1.
Results
Thirteen pts received prior anti-LAG3 (12 with anti–PD-1; 1 with anti–PD-1 + anti–CTLA-4), with a median of 3 prior therapies. Anti-LAG3 was the last therapy prior to TIL therapy in 7 pts; 6 pts had other therapies after anti-LAG3 (eg, chemotherapy, ICI, targeted therapy). Anti-LAG3 was used in 1L in 4 pts; 9 pts received it post-progression. Median duration of anti-LAG3 therapy was 3.3 mo (range, 0.03–9.2 mo). ORR for lifileucel was 38.5% (5 partial responses); 3 responders had primary and 2 acquired resistance to anti-LAG3 + anti–PD-1. Responses were durable, with 60% of responses extending beyond 12 mo. Safety profile was consistent with prior reports; most common (≥30%) grade 3/4 treatment-emergent adverse events were anemia (85%), thrombocytopenia (85%), febrile neutropenia (39%), leukopenia (31%), neutropenia (31%), and lymphopenia (31%).
Conclusions
Lifileucel showed an encouraging 38.5% ORR in pts with advanced melanoma refractory to prior anti-LAG3 + anti–PD-1 ± anti–CTLA-4. Similar to prior observations in pts after anti–PD-1 therapy, both primary and acquired anti-LAG3–resistant pts responded to lifileucel, suggesting that lifileucel outcomes may not be affected by prior anti-LAG3 therapy.
Clinical trial identification
NCT02360579.
Editorial acknowledgement
Medical writing support was provided by Second City Science (Vaniam Group, LLC) and funded by Iovance Biotheraputics, Inc.
Legal entity responsible for the study
Iovance Biotherapeutics, Inc.
Funding
Iovance Biotherapeutics, Inc.
Disclosure
J. Larkin: Financial Interests, Personal, Other, Honoraria: Eisai, Novartis, Incyte , Merck, touchIME, touchEXPERTS, Pfizer, Royal College of Physicians , Cambridge Healthcare Research, RGCP, VJOncology, Agence Unik, BMS, Pierre Fabre, Ipsen, Roche, EUSA Pharma , Aptitude , AstraZeneca, GSK, Calithera, Ultimovacs, Seagen, eCancer, Inselgruppe, Goldman Sachs, MSD; Financial Interests, Personal, Advisory Role, Consulting: iOnctura , Apple Tree, Merck, BMS, Eisai, Debipharm, Incyte; Financial Interests, Institutional, Research Grant: Achilles, BMS, MSD, Nektar, Novartis, Pfizer, Roche, Immunocore, Aveo, Pharmacyclics. S. Dalle: Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Institutional, Advisory Board: MSD. M.F. Sanmamed: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Role, Consulting: Numab, BMS; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Advisory Board: Numab. J.C. Hassel: Financial Interests, Institutional, Research Grant: Clinical Trial Agreement. H. Kluger: Financial Interests, Institutional, Research Grant: Apexigen, BMS, Merck; Non-Financial Interests, Personal, Other, Unpaid relationship: Celldex. M. Orloff: Financial Interests, Personal, Advisory Role, Consulting: Trisalus, Ideaya, Immunocore; Financial Interests, Personal, Advisory Board: Trisalus, Ideaya, Immunocore. J.S. Weber: Financial Interests, Personal, Funding, supports an IIT: BMS; Financial Interests, Personal, Stocks/Shares: Biond, Evaxion , Neximmune, Instil Bio, OncoC4; Financial Interests, Personal, Other, Honoraria: BMS, Merck , Pfizer, AstraZeneca , Regeneron, Incyte, Genentech, Iovance, OncoC4, Sellas, Biond, Instil Bio, Evaxion; Financial Interests, Personal, Advisory Role: BMS, Merck , Pfizer, AstraZeneca , Regeneron, Incyte, Genentech, Iovance, OncoC4, Sellas, Biond, Instil Bio, Evaxion; Financial Interests, Personal, Royalties, named on a CTLA4 biomarker and a TIL growth patent: Moffitt; Financial Interests, Personal, Royalties, named on a PD-1 biomarker patent: Biodesix; Financial Interests, Personal, Other, Travel: BMS. F. Graf Finckenstein: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. P. Hari: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. M. Jagasia: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. H. Yin: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. W. Shi: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. G. Sulur: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. X. Wu: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. V. Gontcharova: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. K. Lewis: Financial Interests, Personal, Advisory Role: Array BioPhar, Merck, Roche, Regeneron, Sanofi, Iovance Biotherapeutics, nektar, Merck; Financial Interests, Personal, Other, Travel: Roche/Genentech, Regeneron, Neon Therapeutics, alkermes; Financial Interests, Personal, Other, Honoraria: Array BioPharma, Iovance Biotherapeutics; Financial Interests, Institutional, Funding: Roche/Genentech, Merck, Array BioPharma, Incyte, Nektar, Iovance Biotherapeutics, Bristol Myers Squibb, Kartos Therapeutics, OncoSec, Regeneron, alkermes, Neon Therapeutics, Ultimovacs, Senhwa Biosciences, Replimune, Amgen, Seattle Genetics; Non-Financial Interests, Personal, Other, Uncompensated Relationships: Roche/Genentech, Regeneron. All other authors have declared no conflicts of interest.