Combination Nivolumab, CD137 Agonism, and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma
Year: 2022
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: Metastatic melanoma is a tumor amenable to immunotherapy in part due to the presence of antigen-specific tumor-infiltrating lymphocytes (TIL). These T cells can be activated and expanded for adoptive cell transfer (ACT), which has resulted in relatively high rates of clinical responses. Similarly, immune checkpoint inhibitors, specifically programmed cell death protein 1 (PD-1) blocking antibodies, augment antitumor immunity and increase the influx of T cells into tumors. Thus, we hypothesized that addition of PD-1 inhibition may improve the outcomes for patients undergoing ACT with TILs. PATIENTS AND METHODS: Patients with stage III/IV metastatic melanoma with unresectable disease who were anti-PD-1 treatment-naïve were enrolled. TILs were generated in the presence of anti-4-1BB antibody in vitro and expanded for ACT. Patients in cohort 1 received TIL infusion followed by nivolumab. Patients in cohort 2 also received nivolumab prior to surgical harvest and during TIL production. RESULTS: A total of 11 patients were enrolled, all of whom were evaluated for response, and nine completed ACT. Predominantly CD8+ TILs were successfully expanded from all ACT-treated patients and were tumor reactive in vitro. The trial met its safety endpoint, as there were no protocol-defined dose-limiting toxicity events. The objective response rate was 36%, and median progression-free survival was 5 months. Two nonresponders who developed new metastatic lesions were analyzed to determine potential mechanisms of therapeutic resistance, which included clonal divergence and intrinsic TIL dysfunction. CONCLUSIONS: Combination therapy with TILs and nivolumab was safe and feasible for patients with metastatic melanoma and provides important insights for future therapeutic developments in ACT with TILs.
Source: Clinical Cancer Research
Authors: MacLean S. Hall, John E. Mullinax, Cheryl A. Cox, Amy M. Hall, Matthew S. Beatty, Jamie Blauvelt, Patrick Innamarato, Luz Nagle, Holly Branthoover, Doris Wiener, Benjamin Schachner, Alberto J. Martinez, Allison D. Richards, Carolyn J. Rich, Marjorie Colón Colón, Michael J. Schell, Jamie K. Teer, Nikhil I. Khushalani, Jeffrey S. Weber, James J. Mulé, Vernon K. Sondak, Shari Pilon-Thomas, Amod A. Sarnaik
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: American Cancer Society, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Celgene, Moffitt Cancer Center, Regeneron Pharmaceuticals, Celldex Therapeutics, Swim Across America, Incyte, Merit Medical Systems, Castle Biosciences, Seagen, National Institutes of Health, EMD Serono, National Cancer Institute
OpenAlex ID: W4304084173