Surufatinib plus toripalimab in advanced soft tissue sarcoma (STS): Results from a multicenter, single-arm, basket study.

42 Background: Soft tissue sarcomas (STS) are highly malignant despite their low incidence and prone to recurrence, with limited therapeutic options after failure of first-line treatment. Several antiangiogenic monotherapies have shown some efficacy but limited benefit. The open-label, multi-cohort, single-arm, basket study was performed to evaluate the efficacy and safety of the combination of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) with toripalimab (an anti-programmed death 1 [PD-1] antibody) for Chinese patients (pts) with advanced solid tumors. Here, we reported the results from the STS cohort. Methods: Pts with STS who had progressed on ≤ 2 lines of systemic chemotherapy, or were intolerant to standard treatment, or for whom there was currently no effective therapy were eligible. They received 21-day cycles of surufatinib 250 mg orally, once daily, plus toripalimab 240 mg intravenously, once every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of data cutoff (Feb 28, 2023), a total of 20 pts (incl. 4 treatment-naïve pts) were enrolled and received the combination treatment (mean duration: 5.81 months [m]). Median (range) age was 50 (23-74) years, 10 pts were male, 17 pts were TNM stage IV. The pathological types include leiomyosarcoma (n=4, incl. 1 naïve patient), synovial sarcoma (n=4), alveolar soft part sarcoma (n=3, incl. 2 naïve pts), undifferentiated pleomorphic sarcoma (n=3), liposarcoma (n=2, incl. 1 naïve patient) and fibrosarcoma (n=1), malignant fibrous histiocytoma (n=1) and others (n=2). Seven (35%) pts had PD-L1 combined positive score of ≥1. The median follow-up duration was 27.14 m. Confirmed ORR and disease control rate (DCR) for 19 efficacy-evaluable pts was 10.5% and 68.4%, respectively; median duration of response was 7.05m. The median progression-free survival (mPFS) and median overall survival (mOS) was 2.69 m and 16.23 m for all dosed pts. For 16 previously treated pts, ORR and DCR was 6.3% and 62.5% respectively; median duration of response (DoR) was 7.13 m; mPFS was 2.65 m; mOS was 14.32 m. 18 (90%) pts experienced at least one treatment-related adverse event (TRAE), and 7 (35%) of them reported grade ≥3 TRAEs. The incidence of immune-related adverse events (irAEs) was 70%, only 2 pts had grade ≥3 irAEs, which were immune-related pancreatitis and immune-related diabetes. 2 pts were permanently discontinued due to TRAEs, which were grade 2 renal impairment and grade 3 hyperglycemia. No new safety signals were observed. Conclusions: Surufatinib plus toripalimab had a promising antitumor activity and a manageable safety profile in pts with advanced STS. Clinical trial information: NCT04169672 .