1086MO - Lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced mucosal melanoma after progression on immune checkpoint inhibitors (ICI): Results from the phase II C-144-01 study

Background

Advanced mucosal melanoma is rare and difficult to treat, with worse outcomes after anti–PD-1 therapy than nonmucosal melanoma (median ORR: 19%–23%; median OS: 11.3–13.4 mo in large pooled analyses [ D’angelo JCO 2017 , Mignard J Oncol 2018 , Hamid Br J Can 2018 ]). Lifileucel, a one-time autologous TIL cell therapy, had an ORR of 31.4% in 153 pts with heavily pretreated advanced melanoma (only uveal excluded) in the C-144-01 study (NCT02360579; Chesney JITC 2022 ). We report outcomes of pts with advanced mucosal melanoma treated with lifileucel in C-144-01.

Methods

Pts (coh 2+4) must have progressed after anti–PD-1/PD-L1 therapy. Pts had ≥1 lesion resected for lifileucel manufacturing, then received lymphodepleting chemotherapy (cyclophosphamide 60 mg/kg/d × 2d; fludarabine 25 mg/m²/d × 5d), a single lifileucel infusion, and up to 6 doses of high-dose IL-2. Responses were assessed by IRC per RECIST v1.1.

Results

Fifteen pts with mucosal melanoma were enrolled; lifileucel was manufactured for all 15 (100%), and lymph nodes were the most common source (47%). Twelve pts received lifileucel (median target lesion SOD: 118.9 mm; median prior lines of therapy: 2 [range: 1–6]; LDH >ULN: 42%; liver and/or brain metastases: 42%). Median number of TIL infused was 26 × 10⁹ cells. ORR was 50% (95% CI: 21%–79%). At median study follow-up of 35.7 months, median DOR was not reached (NR; 95% CI: 12.5 mo–NR), median PFS was NR (95% CI: 1.4 mo–NR), and median OS was 19.4 mo (95% CI: 7.9–NR). TEAEs were consistent with known safety profiles of lymphodepleting chemotherapy and IL-2. The most common (≥30%) G3/4 non-hematologic TEAEs were febrile neutropenia (58%) and hypotension (33%). Translational data will be presented.

Conclusions

In C-144-01, the activity of lifileucel in this small subset of pts with the difficult-to-treat mucosal melanoma subtype was clinically meaningful and durable (ORR: 50%; median DOR: NR) with anti-tumor activity that was consistent with the overall post-anti–PD-1/PD-L1 advanced melanoma population. These data further support the potential benefit of lifileucel as a one-time treatment that is differentiated from other immunotherapies.

Clinical trial identification

Editorial acknowledgement

Writing assistance was provided by Amanda Kelly (Iovance Biotherapeutics, Inc.).

Legal entity responsible for the study

Iovance Biotherapeutics, Inc.

Funding

Iovance Biotherapeutics, Inc.

Disclosure

H. Kluger: Financial Interests, Institutional, Research Funding: Apexigen, BMS, Merck; Financial Interests, Personal, Advisory Role: BMS, Clinigen, Shionogi, Chemocentryx, Calithera, Signatero, Merck, Iovance. S. Thomas: Financial Interests, Personal, Speaker’s Bureau: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One; Financial Interests, Personal, Advisory Role: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One; Financial Interests, Institutional, Research Funding: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One. J.A. Chesney: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; Financial Interests, Institutional, Research Funding: Replimune, Amgen, Iovance Biotherapeutics, Inc., FATE. E. Domingo-Musibay: Financial Interests, Institutional, Other, Grants or contracts: Instil Bio. M.F. Sanmamed: Non-Financial Interests, Personal, Advisory Board: Numab, BMS, Pieris; Non-Financial Interests, Institutional, Research Funding: Roche, BMS; Financial Interests, Personal, Speaker’s Bureau: MSD, Replimune; Financial Interests, Personal, Other, Grant travel: Roche, BMS, AZ. T. Medina: Financial Interests, Personal, Advisory Role: Merck, Bristol Myers Squibb, Iovance Biotherapeutics, Inc., Moderna, Nektar, Regeneron, Exicure, Checkmate, BioAtla, Xencor, Replimune, Day One Pharmaceuticals, Pfizer, Taiga. E. Whitman: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck; Financial Interests, Personal, Speaker’s Bureau: Merck, Bristol Myers Squibb, Regeneron, Castle BioSciences. F. Graf Finckenstein: Financial Interests, Personal, Leadership Role: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Officer: Iovance Biotherapeutics, Inc. J. Chou, X. Wu, G. Sulur, W. Shi: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, Inc. A. Sarnaik: Non-Financial Interests, Institutional, Non-financial benefits: Iovance Biotherapeutics, Inc.; Financial Interests, Institutional, Royalties: Iovance Biotherapeutics, Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: Iovance Biotherapeutics, Inc., Guidepoint, Defined Health, Boxer Capital, Huron Consulting Group, Keyquest Health, Istari, Rising Tide, Gerson Lehram Group; Financial Interests, Personal, Speaker’s Bureau: Society for ImmunoTherapy of Cancer, Physicians' Education Resource, Medscape, WebMD, MedStart Health; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Iovance Biotherapeutics, Inc., Provectus Biopharmaceuticals; Financial Interests, Personal, Other, Patents: Moffitt Cancer Center, Provectus Biopharmaceuticals; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Bristol Myers Squibb, Genentech. All other authors have declared no conflicts of interest.