A phase I/II study of C019199 in combination with sintilimab in advanced malignancy.
Authors: Ye Feng , Zhang Yongchang , Cai Mingquan , Li Jiayi , Sheng Wang , Wang Zhan , Zeng Liang , Li Yibin , Ye Huangyang 
Published: June 2024

e15110 Background: C019199 is an oral CSF-1R/DDRs/VEGFR2 multiple kinase inhibitor and modulates the immune micro-environment of tumor cells. Previous phase I study of C019199 as a mono-therapy for advanced solid tumors has shown promising safety and anti-tumor activity. This phase I/II study is to evaluate the safety and efficacy of the combination of C019199 and Sintilimab in solid tumors. Methods: An open label, multicenter phase I/II study of C019199 combined with Sintilimab is currently enrolling (NCT06220318). Eligible subjects (age of ≥18 years and <76 years) with histologically or cytologically confirmed relapsed, refractory, or progressive metastatic solid tumors will be enrolled in. This trial consists of 2 parts: a phase I dose escalation study using a standard 3+3 design with 3 doses of C019199 (100 mg/qd, 200 mg/qd, 300 mg/qd) combined with a fixed dose of Sintilimab (200 mg, iv, q3w) to determine the maximum tolerated dose (MTD) and recommended phase Ⅱ dose (PR2D); A phase II study is planned to enroll about 20 patients in each tumor type, including but not limited to the following: colorectal cancer, gastric cancer, esophageal squamous cell carcinoma, pancreatic cancer, triple negative breast cancer, head and neck squamous cell carcinoma. Results: A total of 10 patients with advanced solid tumors were enrolled in the phase I study from Jul 20, 2023 to Nov 14, 2023. Median age was 54 (range, 37-71), with 6 males and 4 females. Tumor types were colorectal cancer (7 pts), non-small cell lung cancer (2 pts) and cervical cancer (1 pts), with a median 3 prior systemic therapies (range, 1-7). As of Jan 15, 2024, we have assessed safety in all pts and efficacy in pts with at least one tumor assessment result. No dose-limiting toxicities (DLT) observed in the dose range of 100 mg/qd~300 mg/qd and the MTD has not been reached. The most frequently reported TRAEs were aspartate aminotransferase increased (80%), γ-glutamyltransferase increased (70%), proteinuria (70%), creatine kinase-MB increased (70%), alkaline phosphatase increased (60%). Grade ≥3 TRAEs were hypertension (30%), proteinuria (10%), immune hepatitis (10%), diarrhea (10%). Among 7 colorectal cancer patients, 1 subject had partial responds (PR) and 6 had stable disease (SD) as the best responds with ORR of 14.3%, DCR of 100%. Four subjects were still on treatment. Median PFS was not reached (>3month). Two patients with non-small cell lung cancer and 1 patient with cervical cancer achieved the best response of SD, with a DCR of 100%. Phase II study is ongoing. Recommended dose is 200 mg/qd as the RP2D in selected solid tumors. Conclusions: The combination of C019199 and Sintilimab has shown good overall safety and tolerability. No DLT was observed in the dose range of 100 mg/qd ~ 300 mg/qd. Preliminary anti-tumor activity was observed in patients with advanced solid tumors. Phase II study is ongoing to accumulate more clinical data. Clinical trial information: NCT06220318 .