A phase 1 study of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients with metastatic renal cell cancer.

Abstract

528 Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express the carbohydrate α(1,3)Gal, to which humans have an inherent pre-existing immunity. HAR is designed to leverage this mechanism to educate the immune system towards antigens expressed by the patient’s own tumor cells. Methods: This study is a Phase 1 dose escalation trial of HAR for patients with Renal cell carcinoma (RCC). Eligible patients had recurrent or metastatic RCC with a clear cell component. Trial was a standard 3+3 design with patients receiving weekly intradermal injection of HAR (150 x106 cells/300 x106 cells intradermally) for 4 weeks followed by biweekly injections for 10 weeks. After the initial determination of dose-limiting toxicity, an expansion cohort up to 14 patients was enrolled. The primary endpoint was safety and determination of a maximum tolerated dose (MTD). Secondary endpoints are efficacy and immunological correlates. Results: A total of 18 patients (4 low dose, 14 high dose) were enrolled. The MTD was set at 300 x106 cells intradermally with no dose limiting toxicity (DLT). The most frequently reported adverse events (regardless of attribution), occurring in ≥ 20% of subjects, were abdominal pain, fatigue, pain, and injection site reactions. The most frequently reported laboratory abnormality (regardless of attribution) was anemia in 20% of subjects. There have been 5 reported serious adverse events, none deemed related to HAR. Conclusions: RCC is considered an immunogenic tumor based on its response rate to immune checkpoint blockade and IL-2, occasional spontaneous regression, and the high level of tumor T cell infiltration. HAR was well tolerated in this patient population. Therefore, RCC is an appropriate tumor type to target with combination immunotherapy including HAR. Updated results will be presented. Clinical trial information: NCT02035358.