Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial.

Autor: Vos JL; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Burman B; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jain S; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fitzgerald CWR; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sherman EJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Dunn LA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Fetten JV; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Michel LS; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kriplani A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ng KK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Eng J; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Tchekmedyian V; Department of Medicine, Maine Medical Center-Tufts University School of Medicine, Portland, ME, USA., Haque S; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Katabi N; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kuo F; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Han CY; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Nadeem Z; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Yang W; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Makarov V; Center for Immunotherapy and Precision Immuno-oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Srivastava RM; Center for Immunotherapy and Precision Immuno-oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Ostrovnaya I; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Prasad M; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Zuur CL; Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.; Department of Otorhinolaryngology Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands., Riaz N; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Pfister DG; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Klebanoff CA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chan TA; Center for Immunotherapy and Precision Immuno-oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Ho AL; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. hoa@mskcc.org., Morris LGT; Head and Neck Service and Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. morrisl@mskcc.org.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2023 Dec; Vol. 29 (12), pp. 3077-3089. Date of Electronic Publication: 2023 Aug 24.
DOI: 10.1038/s41591-023-02518-x
Abstrakt: Salivary gland cancers (SGCs) are rare, aggressive cancers without effective treatments when metastasized. We conducted a phase 2 trial evaluating nivolumab (nivo, anti-PD-1) and ipilimumab (ipi, anti-CTLA-4) in 64 patients with metastatic SGC enrolled in two histology-based cohorts (32 patients each): adenoid cystic carcinoma (ACC; cohort 1) and other SGCs (cohort 2). The primary efficacy endpoint (≥4 objective responses) was met in cohort 2 (5/32, 16%) but not in cohort 1 (2/32, 6%). Treatment safety/tolerability and progression-free survival (PFS) were secondary endpoints. Treatment-related adverse events grade ≥3 occurred in 24 of 64 (38%) patients across both cohorts, and median PFS was 4.4 months (95% confidence interval (CI): 2.4, 8.3) and 2.2 months (95% CI: 1.8, 5.3) for cohorts 1 and 2, respectively. We present whole-exome, RNA and T cell receptor (TCR) sequencing data from pre-treatment and on-treatment tumors and immune cell flow cytometry and TCR sequencing from peripheral blood at serial timepoints. Responding tumors universally demonstrated clonal expansion of pre-existing T cells and mutational contraction. Responding ACCs harbored neoantigens, including fusion-derived neoepitopes, that induced T cell responses ex vivo. This study shows that nivo+ipi has limited efficacy in ACC, albeit with infrequent, exceptional responses, and that it could be promising for non-ACC SGCs, particularly salivary duct carcinomas. ClinicalTrials.gov identifier: NCT03172624 .
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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