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Introduction: Dual checkpoint inhibitor therapy with nivolumab and ipilimumab has been FDA-approved for a number of different cancers including melanoma, recurrent NSCLC, and hepatocellular carcinoma. However, their role in the treatment of ACC and other salivary gland carcinomas is not well established. Methods: We performed a Simon’s two-stage prospective single-institution phase II clinical trial of nivolumab (240 mg intravenously every 2 weeks for 16 weeks, then 480 mg every 4 weeks) with ipilimumab (1 mg/kg intravenously every 6 weeks), both of which were provided until intolerable toxicity or disease progression. Two cohorts were analyzed: patients with metastatic/recurrent ACC and patients with other salivary gland cancers. The primary endpoint was median progression-free survival (PFS) based on RECIST and immune-related RECIST (irRECIST) criteria; secondary endpoints were overall response rate (ORR), overall survival (OS), and toxicity. Results: Patients with ACC (n=19) and other salivary gland carcinomas (total n=5; parotid gland adenocarcinoma (n=3), salivary duct carcinoma (n=1), and myoepithelial carcinoma (n=1)) were enrolled between May 2017 and July 2019. Among the patients with ACC, the median OS was 30.0 months (95% confidence interval (CI) 15.3 months to not reached), the median PFS was 8.3 months (95% CI 5.5 - 30.0 months), and the disease control rate (DCR) was 53% (10/19). The ORR in the ACC group was 5% (CR 0%, n=0; confirmed PR 5%, n=1) using both RECIST and irRECIST criteria, with one patient having continued stable disease at the time of trial conclusion. In the salivary gland tumor cohort, the median OS was 10.4 months (95% CI 6.21 months to not reached), the median PFS time was 6.21 months (95% CI 2.83 months to not reached), and the DCR was 40% (2/5). The ORR in this cohort was 0% using both RECIST and irRECIST criteria. Across both cohorts, platelet counts above the joint cohort’s median were significantly associated with better OS (p=0.032) and PFS (p=0.046). Additionally, although not significant, there was a trend for improved OS and PFS among patients with neutrophil-to-lymphocyte ratios >5 (OS p=0.42, PFS p=0.25) and above median neutrophil counts (OS p=0.24, PFS p=0.18). Four patients with ACC underwent circulating tumor DNA sequencing, resulting in the identification of two MYB-NFIB translocations, one NOTCH1 Cys1383 frameshift mutation, one MTOR N1760K mutation, and one PDGFRA copy number gain. Common immune-related toxicities include fatigue (54%), lymphocytopenia (46%), and anemia (42%) with lymphocytopenia being the most common grade III/IV adverse event. Conclusion: In patients with recurrent or metastatic ACC and other salivary gland neoplasms, combination nivolumab with ipilimumab resulted in moderate disease control. Further studies are warranted to validate our findings. Citation Format: Young Kwang Chae, Richard Duan, Liam Il-Young Chung, Youjin Oh, Maria Matsangou, Mark Agulnik, Victoria Villaflor, Devalingam Mahalingam. Phase II study of nivolumab and ipilimumab for treatment of metastatic/recurrent adenoid cystic carcinoma (ACC) of all anatomic sites of origin and other malignant salivary gland tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT165. |
