Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.

Journal Article (Journal Article)

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3-29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer.

Full Text

Duke Authors

Cited Authors

  • Creelan, BC; Wang, C; Teer, JK; Toloza, EM; Yao, J; Kim, S; Landin, AM; Mullinax, JE; Saller, JJ; Saltos, AN; Noyes, DR; Montoya, LB; Curry, W; Pilon-Thomas, SA; Chiappori, AA; Tanvetyanon, T; Kaye, FJ; Thompson, ZJ; Yoder, SJ; Fang, B; Koomen, JM; Sarnaik, AA; Chen, D-T; Conejo-Garcia, JR; Haura, EB; Antonia, SJ

Published Date

  • August 2021

Published In

Volume / Issue

  • 27 / 8

Start / End Page

  • 1410 - 1418

PubMed ID

  • 34385708

Pubmed Central ID

  • PMC8509078

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/s41591-021-01462-y


  • eng

Conference Location

  • United States