An open-label phase 1b/2 study of surufatinib in combination with tislelizumab in subjects with advanced solid tumors.
Authors: Dasari Arvind , Kauh John S. , Tucci Christopher , Nanda Shivani , Kania Marek K. , Carlisle Jennifer W , Paulson Andrew Scott 
Published: June 2021

TPS2677 Background: Surufatinib (S) is an inhibitor of VEGFR1, 2, & 3; FGFR1; and CSF-1R. In two phase 3 randomized trials (SANET-ep; NCT02588170 & SANET-p; NCT02589821) S demonstrated a manageable safety profile and statistically significant efficacy. Patients (pts) with extrapancreatic neuroendocrine tumors (epNETs) achieved a median progression free survival (PFS) of 9.2 v 3.8 months (mo) (hazard ratio [HR] 0.334; p<0.0001), and pts with pancreatic NETs (pNETs) achieved a median PFS of 10.9 v 3.7 mo (HR 0.491; p=0.0011), with S v placebo, respectively. S was recently approved for the treatment of pts with epNET in China. Tislelizumab (T) is a humanized immunoglobulin G4 anti-PD-1 monoclonal antibody engineered to minimize binding to Fc-gamma-receptor on macrophages. T is approved in China in combination with chemotherapy for squamous non-small cell lung cancer and has conditional approval for Hodgkin’s lymphoma and locally advanced or metastatic urothelial carcinoma with PD-L1 high expression. The objective of this study is to evaluate the safety and efficacy of combination therapy with S and T, which may have synergistic effects, where inhibition of angiogenesis along with stimulation of an immune response may enhance the overall antitumor activity. Methods: This study (NCT04579757) will include pts, ≥18 years of age, with advanced metastatic solid tumors, who have an Eastern Cooperative Oncology Group performance status of 0 or 1 and have progressed on or are intolerant to standard therapies. The primary objective of part 1 (dose escalation) will be to evaluate the safety and tolerability of S and T to determine the recommended phase 2 dose of the combination. The starting dose in part 1 will be 250 mg of S, orally, daily, and 200mg of T, intravenously, every 3 weeks. The dose of S will be escalated during part 1, while the dose of T will remain fixed. Endpoints include dose limiting toxicities, treatment emergent adverse events, serious adverse events, adverse events leading to discontinuation, electrocardiograms, clinical laboratory abnormalities and vital signs. Antitumor activity will be evaluated as a secondary objective. Six to 12 pts will be enrolled. The primary objective of part 2 (dose expansion) will be to evaluate the objective response rate (ORR) of S in combination with T per RECIST v1.1. The endpoint will be ORR at 12 weeks. Key secondary endpoints include PFS, disease control rate, duration of response, safety endpoints, and PK parameters. Approximately 95 pts with indications of interest will be enrolled: colorectal cancer, neuroendocrine tumors (thoracic and gastroenteropancreatic), small-cell lung cancer, gastric cancer, and soft tissue sarcoma (undifferentiated pleomorphic sarcoma and alveolar soft part sarcoma). Enrollment in the United States is open and ongoing, and enrollment in Europe is planned for fourth quarter 2021. Clinical trial information: NCT04579757.