A phase II trial cohort of nivolumab plus ipilimumab in patients (Pts) with recurrent/metastatic salivary gland cancers (R/M SGCs).

Abstract

6002 Background: R/M SGCs are a diverse group of malignant neoplasms arising from the major or minor salivary glands and have no standard treatment. The impact of combining PD-1/CTLA-4 checkpoint blockade in R/M SGCs is unknown. Methods: In a Simon's two-stage minimax phase II trial, pts with progressive R/M SGCs (any histology except adenoid cystic carcinoma (ACC)) were enrolled and treated with nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (1 cycle = 6 weeks). Imaging, using RECIST v1.1 response assessment, was scheduled to be performed approximately every 12 weeks. The primary endpoint was best overall response (BOR = complete response [CR]+partial response [PR]) per RECIST v1.1. To detect a difference between an unacceptable BOR of 5% and a desirable BOR of 20% (one-sided type I error of 10%, power of 90%), at least 1 in the first 18 pts required an observed response. At least 4 responses of 32 total pts were needed to meet the primary endpoint. Treatment beyond progression of disease (PD) was allowed at the discretion of the investigator. A second cohort of pts with ACC was analyzed and reported separately. Results: From 7/25/2017-7/16/2020, 32 pts were enrolled and evaluable for the primary endpoint. There was 3 confirmed PRs in the first 18 pts, therefore enrollment of the second stage continued. BOR rate was 16% (5/32). Seven pts never reached a first disease assessment and were classified as non-responders: 5 due to clinical PD, 1 due to toxicity, and 1 pt withdrew. Four pts discontinued the trial for toxicities: pancytopenia (1), blurry vision (1), cardiomyopathy/hyperglycemia (1), and neutropenic sepsis (1), and mucositis (1). The 5 confirmed responders had regressions ranging from -66% to -100% in target lesions, with a duration of therapy ranging from 15.7 to 29.5 months (treatment ongoing for one as of 2/6/20). Conclusions: This cohort met its primary endpoint, and the responses observed were dramatic and durable. Paired biopsy and peripheral blood samples will be analyzed to elucidate insights into mechanisms of response and resistance to dual checkpoint blockade. Clinical trial information: NCT03172624.