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 .

• Authors: Joris L Vos, Bharat Burman, Swati Jain, Conall W R Fitzgerald, Eric J Sherman, Lara A Dunn, James V Fetten, Loren S Michel, Anuja Kriplani, Kenneth K Ng, Juliana Eng, Vatche Tchekmedyian, Sofia Haque, Nora Katabi, Fengshen Kuo, Catherine Y Han, Zaineb Nadeem, Wei Yang, Vladimir Makarov, Raghvendra M Srivastava, Irina Ostrovnaya, Manu Prasad, Charlotte L Zuur, Nadeem Riaz, David G Pfister, Christopher A Klebanoff, Timothy A Chan, Alan L Ho, Luc G T Morris
• Journal: Nature medicine (Nat Med) Vol. 29 Issue 12 Pg. 3077-3089 (Dec 2023) ISSN: 1546-170X [Electronic] United States
• PMID: 37620627 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Nivolumab
• Ipilimumab
• Receptors, Antigen, T-Cell

Topics

• Humans
• Nivolumab (adverse effects)
• Ipilimumab (therapeutic use)
• Carcinoma
• Salivary Gland Neoplasms (drug therapy, genetics, chemically induced)
• Receptors, Antigen, T-Cell
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)