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778 TILVANCE-301, a phase 3 study of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy combined with pembrolizumab (pembro) vs pembro alone in treatment-naïve unresectable or metastatic melanoma
  1. Daniel J Olson1,
  2. James Larkin2,
  3. Young Hong3,
  4. Sajeve Thomas4,
  5. Juan Martin-Liberal5,
  6. Andrew JS Furness2,
  7. Patrick Terheyden6,
  8. Gino K In7,
  9. Andrew S Poklepovic8,
  10. Yazan Samhouri9,
  11. Philip Lammers10,
  12. Victoria Atkinson11,
  13. Ryan H Nguyen12,
  14. Idit Peretz13,
  15. Marcus Butler14,
  16. Friedrich Graf Finckenstein15,
  17. Jeffrey Chou15,
  18. Xiao Wu15,
  19. Giri Sulur15,
  20. Wen Shi15 and
  21. John B Haanen16,17,18
  1. 1University of Chicago, Chicago, IL, USA
  2. 2The Royal Marsden NHS Foundation Trust, London, Chelsea, UK
  3. 3Cooper University Hospital, Camden, NJ, USA
  4. 4Orlando Health Cancer Institute, Orlando, FL, USA
  5. 5ICO L’Hospitalet – Hospital Duran i Reynals, Barcelona, Spain
  6. 6University of Lübeck, Lübeck, Germany
  7. 7University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  8. 8Virginia Commonwealth University, Richmond, VA, USA
  9. 9Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA
  10. 10Baptist Cancer Center, Memphis, TN, USA
  11. 11Greenslopes Private Hospital, Greenslopes, QLD, Australia
  12. 12University of Illinois Hospital and Health Sciences System, Chicago, IL, USA
  13. 13Rabin Medical Center, PPDS, Beilinson, Israel
  14. 14Princess Margaret Cancer Centre, Toronto, ON, Canada
  15. 15Iovance Biotherapeutics, Inc, San Carlos, CA, USA
  16. 16Netherlands Cancer Institute, Amsterdam, Netherlands
  17. 17Leiden University Medical Center, Leiden, Netherlands
  18. 18Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland


Background Novel early-line therapies for advanced (unresectable or metastatic) melanoma are needed to improve the rate of deep and durable responses and increase the proportion of patients with long-term benefit. TILVANCE-301 will evaluate the efficacy and safety of lifileucel autologous TIL cell therapy + pembrolizumab (pembro) in patients with untreated advanced melanoma.

Methods TILVANCE-301 (NCT05727904) is a phase 3, multicenter, randomized, open-label, parallel group study that will randomize ~670 patients (1:1; Day 0) to Arm A: lifileucel + pembro (Day 3: tumor tissue resection for TIL manufacturing; Day 5: pembro 200 mg; Day 26: pembro 400 mg; Day 28–29: cyclophosphamide 60 mg/kg; Day 28–32: fludarabine 25 mg/m2; Day 33: lifileucel; Day 34–37: ≤6 doses of high-dose IL-2; Week 10: pembro 400 mg Q6W) or Arm B: pembro alone (same pembro dosing as Arm A). Patients in Arm B with confirmed progressive disease verified by blinded independent review committee (BIRC) have the option to receive lifileucel monotherapy as immediate next treatment and may continue pembro until start of lymphodepleting chemotherapy.

Eligible adults have histologically confirmed advanced melanoma, ECOG PS 0–1, estimated life expectancy >6 mo, ≥1 resectable lesion to generate lifileucel, and ≥1 remaining measurable lesion. Prior neoadjuvant or adjuvant treatment including immune checkpoint inhibitors may be allowed. Prior therapy for metastatic disease, symptomatic untreated brain metastases, organ allograft or prior cell therapy, uveal/ocular melanoma, and chronic systemic steroid therapy are not permitted.

The dual primary efficacy endpoints are BIRC-assessed (RECIST v1.1) ORR and PFS. Key secondary efficacy endpoint is OS. Additional secondary efficacy endpoints include BIRC-assessed CR rate, DOR, and EFS; investigator-assessed ORR, PFS, CR rate, DOR, EFS, and PFS2; and safety as characterized by severity and seriousness of TEAEs, and relationship to study drug. Exploratory endpoints include in vivo T-cell persistence (unique CDR3 sequences in PBMC over time) and correlative biomarkers (eg, lifileucel phenotypic and functional characteristics; lifileucel, tumor, and PBMC gene expression profiles; tumor mutational landscape).

The study will enroll globally, with initial sites in Europe, North America, and Australia.

Acknowledgements Medical writing support was provided by Amanda Kelly (Iovance Biotherapeutics, Inc).

Trial Registration NCT05727904

Ethics Approval The study was approved by the institutional review board at each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines of the International Conference on Harmonization. All patients provided written informed consent.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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