Nivolumab plus ipilimumab in advanced salivary gland cancer: A phase 2 trial Journal Article
| Authors: | Vos, J. L.; Burman, B.; Jain, S.; Fitzgerald, C. W. R.; Sherman, E. J.; Dunn, L. A.; Fetten, J. V.; Michel, L. S.; Kriplani, A.; Ng, K. K.; Eng, J.; Tchekmedyian, V.; Haque, S.; Katabi, N.; Kuo, F.; Han, C. Y.; Nadeem, Z.; Yang, W.; Makarov, V.; Srivastava, R. M.; Ostrovnaya, I.; Prasad, M.; Zuur, C. L.; Riaz, N.; Pfister, D. G.; Klebanoff, C. A.; Chan, T. A.; Ho, A. L.; Morris, L. G. T. |
| Article Title: | Nivolumab plus ipilimumab in advanced salivary gland cancer: A phase 2 trial |
| Abstract: | 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. |
| Keywords: | genetics; clinical trial; antineoplastic agent; ipilimumab; phase 2 clinical trial; antineoplastic combined chemotherapy protocols; receptors, antigen, t-cell; carcinoma; salivary gland tumor; salivary gland neoplasms; lymphocyte antigen receptor; nivolumab; humans; human |
| Journal Title: | Nature Medicine |
| Volume: | 29 |
| Issue: | 12 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-12-01 |
| Start Page: | 3077 |
| End Page: | 3089 |
| Language: | English |
| DOI: | 10.1038/s41591-023-02518-x |
| PUBMED: | 37620627 |
| PROVIDER: | scopus |
| PMCID: | PMC11293616 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK authors are Alan L. Ho and Luc G. T. Morris -- Source: Scopus |
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