119O - Long-term efficacy and patterns of response of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study

Background

The large proportion of patients (pts) with advanced (unresectable or metastatic) melanoma resistant to immune checkpoint inhibitors (ICI) define a significant unmet need. Lifileucel, a one-time autologous TIL cell therapy, has demonstrated durable clinical benefit in this setting, with the C-144-01 study showing an ORR of 31.4% in a heavily pre-treated population. We report 4-year follow-up data from C-144-01 on lifileucel’s treatment outcomes and patterns of response.

Methods

C-144-01 (NCT02360579) is a prospective, open-label, multicohort, nonrandomized phase 2 study; data from pts in Cohorts 2 and 4 are presented. Pts had ≥1 lesion(s) resected (≥1.5 cm diameter) for 22-day cryopreserved lifileucel manufacturing. The treatment regimen consisted of nonmyeloablative lymphodepletion (cyclophosphamide 60 mg/kg/d × 2d, fludarabine 25 mg/m2/d × 5d), followed by a single lifileucel infusion and ≤6 doses of high-dose IL-2 (600,000 IU/kg).

Results

As of data cutoff (30 June 2023), 153 pts were assessed; median study follow-up was 48.1 months. Independent review committee-assessed ORR by RECIST v1.1 was 31.4% with median DOR (months) of NR. The 1-, 2-, 3-, and 4-year OS rate was 54.0%, 33.9%, 28.4%, and 21.9%, respectively. Responders (n=48) had a median age of 55.0 years with median of 3 prior lines of therapies. Clinically meaningful 4-year OS rates were seen across all patterns of response (range, 37.2%–68.2%; Table); pts with deepened response had numerically higher OS rate. Treatment-emergent adverse events were consistent with known safety profiles of lymphodepletion and IL-2. Table: 119O

OS and DOR by patterns of response

^aPatients with CR or PR on Day 42 visit. ^bPatients with CR or PR after Day 42 visit. ^cPatients who had SD and improved to confirmed PR or had PR and improved to confirmed CR. CI, confidence interval; CR, complete response; DOR, duration of response; OS, overall survival; PR, partial response; SD, stable disease.

Conclusions

In this 4-year analysis of heavily pretreated pts with advanced melanoma, treatment with lifileucel produced durable efficacy, leading to long-term survival benefit across different patterns of responders.

Clinical trial identification

NCT02360579; first posted on 10 February, 2015.

Editorial acknowledgement

Under the direction of the authors, Peloton Advantage, Llc, an OPEN Health company, provided medical writing and editorial support.

Legal entity responsible for the study

Iovance Biotherapeutics, Inc.

Funding

Iovance Biotherapeutics, Inc.

Disclosure

T. Medina: Financial Interests, Personal, Advisory Role, Consulting/Advisory: Merck, BMS, Iovance Biotherapeutics, Moderna, Nektar, Regeneron, Exicure, Checkmate, BioAtla, Xencor, Replimune, Day One Pharmaceutical, Pfizer, Taiga. E. Whitman: Financial Interests, Personal, Advisory Role, Consulting/Advisory: Merck; Financial Interests, Personal, Speaker’s Bureau: Merck, BMS, Regeneron, Castle BioSciences. H. Kluger: Financial Interests, Personal, Research Funding: Apexigen, BMS, Merck; Financial Interests, Personal, Advisory Role, Consulting/Advisory: BMS, Clinigen, Shionogi, Chemocentryx, Calithera, Signatero, Merck, Iovance Biotherapeutics. 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, Consulting/Advisory: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One; Financial Interests, Personal, Research Funding: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One. A. Sarnaik: Financial Interests, Personal, Royalties, Royalties and Licenses: Iovance Biotherapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: Iovance Biotherapeutics, Guidepoint, Defined Health, Boxer Capital, Huron Consulting Group, KeyQuest Health, Istari, Rising Tide, Second City Science, Market Access, Gerson-Lehram Group; Financial Interests, Personal, Other, Honoraria: Society for Immunotherapy of Cancer, Physician’s Education Resource, Medscape, WebMD, Medstar Health; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Iovance Biotherapeutics, Provectus Biopharmaceuticals; Financial Interests, Personal, Other, Patents: Moffit Cancer Center; Financial Interests, Personal, Advisory Board, Patents: Provectus Biopharmaceuticals; Financial Interests, Personal, Other, Receipt of Equipment, Materials, Drugs, Medical Writing, Gifts, or Other Services: BMS, Genentech. J.M. Kirkwood: Financial Interests, Personal, Advisory Role, Consulting/Advisory: Ankyra Therapeutics, Applied Clinical Intelligence LLC, Axio Research LLC, Bristol Myers Squibb, Cancer Study Group, Checkmate Pharmaceuticals, CytomX Therapeutics, DermTech, iOnctura, Iovance Biotherapeutics, IQVIA, Istari Oncology, Jazz Pharmaceuticals, Lytix Biopharma , AS, Magnolia Innovation LLC, Merck, Natera Inc., Novartis Pharmaceuticals, OncoCyte Corporation, PathAI Inc., Pfizer Inc., Regeneron Pharmaceuticals Inc., Replimune Inc., Scopus BioPharma Inc., Takeda; Financial Interests, Personal, Research Funding: Amgen Inc., Bristol Myers Squibb, Checkmate Pharmaceuticals, Harbour BioMed, Immvira Pharma Co., Immunocore Ltd., Iovance Biotherapeutics, Lion Biotechnologies Inc., Novartis Pharmaceuticals, Takeda, Verastem Inc. J. Larkin: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen, Goldman Sachs, eCancer, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, RGCP, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. J.S. Weber: Financial Interests, Personal, Advisory Board, Ad Boards: BMS; Financial Interests, Personal, Advisory Board: Merck, GSK, Incyte, Genentech, Pfizer, Biond, OncoC4, AstraZeneca, Regeneron, ImCheck, Novartis; Financial Interests, Personal, Stocks/Shares: Biond, Evaxion, Instil Bio, OncoC4; Financial Interests, Personal, Royalties: Moffitt Cancer Center; Financial Interests, Institutional, Local PI: BMS, Regeneron; Financial Interests, Institutional, Coordinating PI: Merck, Novartis; Non-Financial Interests, Personal, Principal Investigator: Moderna, BMS; Non-Financial Interests, Personal, Member: ASCO. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, BeiGene, Bioatla, Eisai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, Nextcure, Novartis, Obsidian, Pfizer, Roche Genentech, SEAGEN, Sanofi / Regeneron, Tempus, Vial, Zelluna; Financial Interests, Personal, Invited Speaker: BMS, Immunocore, Novartis, Pfizer, Sanofi / Regeneron; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Institutional, Local PI: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, Rubius, Seagen, Sanofi / Regeneron, Torque, Zelluna. M. Wermke: Financial Interests, Personal, Other, Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Bristol Myers Squibb, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, immatics, Bayer, ImCheck therapeutics; Financial Interests, Institutional, Research Funding: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Bristol Myers Squibb, Amgen, GEMoaB, Sanofi/Aventis, immatics, Merck Serono; Financial Interests, Personal, Officer, Travel, Accommodations, Expenses: AstraZeneca. F. Graf Finckenstein: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Iovance Biotherapeutics; Financial Interests, Personal, Royalties, Patents, Royalties, Other Intellectual Properties: BMS. J. Chou, B. Gastman, G. Sulur, X. Wu, W. Shi: Financial Interests, Personal, Full or part-time Employment: Iovance Biotherapeutics; Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Iovance Biotherapeutics. E. Domingo-Musibay: Financial Interests, Personal, Research Grant, Grants or Contracts: Instil Bio. All other authors have declared no conflicts of interest.