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492 Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancers
  1. David O’Malley1,
  2. Sylvia Lee2,
  3. Amanda Psyrri3,
  4. Ammar Sukari4,
  5. Sajeve Thomas5,
  6. Robert Wenham6,
  7. Helen Gogas7,
  8. Amir Jazaeri8,
  9. Bradley Monk9,
  10. Peter Rose10,
  11. Antonio Reuda11,
  12. Friedrich Graf Finckenstein12,
  13. Madan Jagasia12,
  14. Rana Fiaz12,
  15. Brigid Garelik12,
  16. Wen Shi12,
  17. Anjali Desai12,
  18. Giri Sulur12,
  19. Guang Chen12,
  20. Xiao Wu12 and
  21. Antonio Jimeno13
  1. 1Ohio State University, Columbus, OH, USA
  2. 2Fred Hutchinson Cancer Center, Seattle, WA, USA
  3. 3Attikon University General Hospital, Athens, Greece
  4. 4Karmanos Cancer Institute, Detroit, MI, USA
  5. 5Orlando Health Cancer Institute, Orlando, FL, USA
  6. 6Moffitt Cancer Center, Tampa, FL, USA
  7. 7Natl. and Kapodistrian University of Athen, Athens, Greece
  8. 8MD Anderson Cancer Center, HOUSTON, TX, USA
  9. 9Arizona Oncology (US Oncology Network), Phoenix, AZ, USA
  10. 10Cleveland Clinic, Columbud, OH, USA
  11. 11Hospital Regional Universitario de Malag, Malaga, Spain
  12. 12Iovance Biotherapeutics, Inc., San Carlos, CA, USA
  13. 13Univ. of Colorado School of Medicine, Aurora, CO, USA


Background Immune checkpoint inhibitors (ICI) are standard-of-care in the treatment of several types of cancer; however, an unmet medical need exists for early-line combination therapies that are able to provide higher response rates, more durable responses, and manageable long-term safety. Lifileucel (LN-144) and LN-145, adoptive cell therapies using tumor-infiltrating lymphocytes (TIL), have demonstrated encouraging efficacy with acceptable safety in patients with advanced cancer that has failed ICI.1–2 To improve efficacy and safety of early-line treatment options, we explored a combination of TIL and pembrolizumab in patients with ICI-naïve melanoma, head and neck squamous cell carcinoma (HNSCC), and cervical cancer.

Methods IOV-COM-202 (NCT03645928) and C-145-04 (NCT03108495) are ongoing Phase 2 multicenter, multicohort, prospective, open-label studies evaluating TIL cell therapy in ICI-naïve patients with solid tumors. We report efficacy and safety from IOV-COM-202 (Cohort 1A: lifileucel and pembrolizumab in patients with unresectable or metastatic melanoma; Cohort 2A: LN-145 and pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC) and C-145-04 (Cohort 3: LN-145 and pembrolizumab in patients with stage 4b, persistent or recurrent cervical cancer who have not received prior systemic therapy). Eligibility across cohorts included ECOG PS ≤1, ≥1 resectable lesion (diameter ≥1.5 cm post-resection) for TIL manufacturing, and ≥1 measurable lesion for response assessment (by investigator per RECIST v1.1). Lifileucel and LN-145 are cryopreserved TIL infusion products generated at central GMP facilities in a 22-day process. Treatment included tumor resection for TIL manufacturing, followed by 1 dose of pembrolizumab, nonmyeloablative lymphodepletion (cyclophosphamide and fludarabine), TIL infusion, ≤6 interleukin-2 doses (600,000 IU/kg IV), and continued pembrolizumab for ≤24 months.

Results As of 09July2021, 32 patients received TIL and pembrolizumab (full-analysis set [FAS]; table 1). Across all cohorts, the objective response rate (ORR) in the FAS was 56.3% (Cohort 1A [melanoma], 87.5%; Cohort 2A [HNSCC], 42.9%; Cohort 3 [cervical], 50.0%; figure 1). Among confirmed responders (n=17), 10 responses (58.8%) were ongoing at data cutoff, with a median study follow-up of 9.7 months. The treatment-emergent adverse-event (TEAE) profile was consistent with the underlying diseases and known profiles of pembrolizumab, nonmyeloablative lymphodepletion, and interleukin-2. The most common (≥30%) Grade ≥3 TEAEs were thrombocytopenia (53.1%), anemia (50.0%), neutropenia (46.9%), and febrile neutropenia (43.8%).

Conclusions The observed efficacy, including ORR and CR rate, and acceptable safety profile are encouraging and warrant continued investigation of the combination of TIL and pembrolizumab in early-line treatment of patients with advanced cancer. Enrollment is ongoing; updated data will be presented.

Acknowledgements This study and analysis were funded by Iovance Biotherapeutics, Inc. (San Carlos, CA, USA). Writing support was provided by Amanda Kelly (Iovance); graphics support was provided by Cognition Studio (Seattle, WA, USA).

Trial Registration NCT03645928 and NCT03108495


  1. Sarnaik AA, et al. J Clin Oncol 2021; doi: 10.1200/JCO.21.00612.

  2. Jazaeri AA, et al. J Clin Oncol 2019;37 (suppl; abstract 182).

  3. Jimeno A, et al. J Immunother Cancer 2020;8 (suppl; abstract 353).

Ethics Approval The IOV-COM-202 study was approved by Advarra Institutional Review Board, approval number Pro00035064; the C-145-04 was approved by WIRB Copernicus Group, approval number 7-1425772-1. All study participants provided written consent via signature of the IRB-approved informed consent form.

Abstract 492 Table 1

Baseline demographic and clinical characteristics and efficacy

Abstract 492 Figure 1

Best percentage change from baseline in target lesion sum of diameters for efficacy-evaluable set*

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