Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial
Benjamin C Creelan, Chao Wang, Jamie K Teer, Eric M Toloza, Jiqiang Yao, Sungjune Kim, Ana M Landin, John E Mullinax, James J Saller, Andreas N Saltos, David R Noyes, Leighann B Montoya, Wesley Curry, Shari A Pilon-Thomas, Alberto A Chiappori, Tawee Tanvetyanon, Frederic J Kaye, Zachary J Thompson, Sean J Yoder, Bin Fang, John M Koomen, Amod A Sarnaik, Dung-Tsa Chen, Jose R Conejo-Garcia, Eric B Haura, Scott J Antonia, Benjamin C Creelan, Chao Wang, Jamie K Teer, Eric M Toloza, Jiqiang Yao, Sungjune Kim, Ana M Landin, John E Mullinax, James J Saller, Andreas N Saltos, David R Noyes, Leighann B Montoya, Wesley Curry, Shari A Pilon-Thomas, Alberto A Chiappori, Tawee Tanvetyanon, Frederic J Kaye, Zachary J Thompson, Sean J Yoder, Bin Fang, John M Koomen, Amod A Sarnaik, Dung-Tsa Chen, Jose R Conejo-Garcia, Eric B Haura, Scott J Antonia
Abstract
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.
Conflict of interest statement
Competing Interest Statement
The remaining authors have no relevant conflicts to disclose.
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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Source: PubMed