Article Text

Download PDFPDF

458 First phase 2 results of autologous tumor-infiltrating lymphocyte (TIL; LN-145) monotherapy in patients with advanced, immune checkpoint inhibitor-treated, non-small cell lung cancer (NSCLC)
  1. Adam Schoenfeld1,
  2. Sylvia Lee2,
  3. Luis Paz-Ares3,
  4. Bernard Doger4,
  5. Scott Gettinger5,
  6. Simon Haefliger6,
  7. Angela Orcurto7,
  8. Ammar Sukari8,
  9. Sophie Papa9,
  10. Juan Francisco Rodriguez Moreno10,
  11. Friedrich Graf Finckenstein11,
  12. Madan Jagasia11,
  13. Rana Fiaz11,
  14. Giri Sulur11,
  15. Guang Chen11,
  16. Viktoria Gontcharova11 and
  17. Kai He12
  1. 1Memorial Sloan Kettering Cancer Center, New York, NY, USA
  2. 2Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  3. 3Hospital Universitario 12 de Octubre, Madrid, Spain
  4. 4Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain
  5. 5Yale Cancer Center, New Haven, CT, USA
  6. 6Universitätsspital Bern, Bern, Switzerland
  7. 7Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  8. 8Karmanos Cancer Institute, Detroit, MI, USA
  9. 9Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  10. 10Hospital Universitario HM Sanchinarro, Madrid, Spain
  11. 11Iovance Biotherapeutics, Inc., San Carlos, CA, USA
  12. 12Ohio State University, Columbus, OH, USA


Background A majority of patients with advanced NSCLC develop disease progression with first-line immune-checkpoint inhibitors (ICI) ± chemotherapy. In the setting of ICI resistance, effective strategies to provide deep and durable responses are urgently needed. Lifileucel (LN-144) and LN-145 are centrally manufactured (cryopreserved drug-product, 22-day manufacturing process) autologous TIL products that have demonstrated activity in advanced melanoma, cervical cancer, and head and neck carcinoma.1–4 Here, we report the first safety and efficacy data for LN-145 as monotherapy in patients with advanced NSCLC.

Methods IOV-COM-202 (NCT03645928) is a phase 2 multicenter, multicohort, open-label study evaluating autologous TIL cell therapy in patients with solid tumors. We report data from Cohort 3B, investigating LN-145 monotherapy in patients with advanced or metastatic NSCLC. Eligibility required 1–3 prior lines of systemic therapy, including either ICI or oncogene-directed therapy. Treatment included nonmyeloablative lymphodepletion, TIL infusion, and ≤6 interleukin-2 doses. Primary endpoints were safety (incidence of Grade ≥3 treatment-emergent adverse events [TEAEs]) and objective response rate (ORR, investigator-assessed using RECIST v1.1). Exploratory biomarker analyses, including T-cell receptor (TCR) repertoire, were performed.

Results As of 24June2021, 28 patients received LN-145 (full-analysis set [FAS]; table 1) and 24 were efficacy-evaluable; all had received prior ICI. TIL were most commonly harvested from lung metastases (57.1%). Safety was consistent with the underlying disease and known TEAE profiles of nonmyeloablative lymphodepletion and interleukin-2. Grade ≥3 TEAEs in ≥30% of patients were thrombocytopenia and anemia. The ORR in the FAS and efficacy-evaluable set was 21.4% (6/28) and 25.0% (6/24; figure 1), respectively. Median duration of response was not reached and 83% (5/6) of responses were ongoing at last follow-up (median study follow-up, 8.2 months). One patient had a complete metabolic response, ongoing at 20.7 months; 2 responses occurred in patients who were PD-L1–negative. All responders received ≥2 prior lines of systemic therapy. Twenty-six patients had TIL available from the final drug-product for TCR repertoire analysis; mean (min-max) number of unique TCR clones was 13,142 (3093–35,734) and Shannon Entropy index was 7.34 (3.7–12). Updated data will be presented.

Abstract 458 Figure 1

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

Abstract 458 Table 1

Baseline patient demographic and clinical characteristics; efficacy parameters

Conclusions LN-145 was successfully manufactured and one-time treatment produced an expected safety profile and durable responses in heavily pretreated patients with NSCLC, regardless of PD-L1 expression. The activity of LN-145 monotherapy is encouraging and warrants further investigation of LN-145 as a single-agent and in combination in patients with NSCLC in ongoing studies IOV-LUN-202 (NCT04614103) and IOV-COM-202 Cohorts 3A and 3C (3B closed to enrollment).

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


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

  2. . Thomas SS, et al. J Clin Oncol 2021;39: (suppl; abstract 9537).

  3. Jazaeri A, et al. J Clin Oncol 2019;37: (suppl; abstract 2538).

  4. Jimeno A, et al. J Immunother Cancer 2020;8: (suppl; abstract A378).

Ethics Approval The study was approved by Advarra Institutional Review Board, approval number Pro00035064 and all study participants provided written consent via signature of the IRB-approved Informed Consent form.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.