Surufatinib in US patients with soft tissue sarcoma.

11557 Background: Surufatinib is an inhibitor of VEGFR1, 2, & 3, FGFR1, and CSF-1R. A manageable safety profile, and statistically significant improvement in progression-free survival (PFS) in patients (pts) treated with surufatinib have previously been demonstrated in pts with advanced NETs of extrapancreatic (epNET) and pancreatic (pNET) origin in 2 phase 3 randomized trials conducted in China (SANET-ep; NCT02588170 & SANET-p; NCT02589821). Similar safety and efficacy were demonstrated in this phase 1 study (NCT02549937) in pts with NETs. Here we report the results of surufatinib in pts with soft tissue sarcoma. Methods: This study is a phase 1, dose escalation (ESC)/expansion (EXP) study to evaluate the safety and efficacy of surufatinib in the US and Europe (EXP only). ESC previously reported the recommended phase 2 dose as 300mg once daily. Enrollment into advanced, adult, soft tissue sarcoma EXP cohorts is ongoing. The primary endpoint is PFS rate at 4 months (mo). Soft tissue sarcoma histological subtypes include: angiosarcoma (AS), epithelioid sarcoma (ES), leiomyosarcoma (LMS), pigmented villonodular synovitis (PVNS), synovial sarcoma (SS) and undifferentiated pleomorphic sarcoma (UPS). Results: 32 adults with soft tissue sarcoma were enrolled (2 each AS and ES; 10 LMS; 1 PVNS; 9 SS; 8 UPS). The median age across all subtypes was 56.5 years (range 26-77), and the majority of pts were female (68.8%). 59.3% of pts received ≥ 3 prior lines of therapy (Tx) (median lines of Tx: 3 [range 1-6]). As of 15 Nov 2021, 1 pt (PVNS) remained on Tx. The PFS rate at 4 mo was 17.5%. The median PFS was 2.56 mo (95% CI; 0.92-2.92). The median duration on treatment (mDoT) for all pts was 11.2 weeks (wks) (0.4-39.0). The mDoT for LMS pts was 11.6 wks (3.1-36.0), mDoT for SS pts was 11.9 wks (0.4-27.9), and mDoT for UPS pts was 8.2 wks (2.7-27.9). Of 29 pts with ≥ 1 post baseline assessment, 6 pts (20.7%) achieved stable disease of ≥ 8.0 wks from start of Tx. No pts achieved a partial or complete response. The safety profile of surufatinib remains consistent with previously completed trials. All pts (n = 32) reported ≥ 1 adverse event (AE), and 21 pts (65.6%) reported AEs ≥ grade 3. The most common AEs of any grade were fatigue (53.1%), hypertension (43.8%), diarrhea (40.6%), anemia (25.0%), blood bilirubin increase (25.0%), headache (21.9%), and proteinuria (21.9%). The most commonly reported AEs ≥ grade 3 in > 1 pt were hypertension (21.9%), fatigue (12.5%), and anemia (9.4%). AEs leading to Tx discontinuation occurred in 9.4% of pts. Conclusions: Surufatinib demonstrated minimal antitumor activity as a single agent in heavily pretreated pts across various types of soft tissue sarcoma. The safety profile in pts with soft tissue sarcoma remains consistent with previously reported and ongoing studies with surufatinib. Clinical trials are ongoing with surufatinib globally, with active recruitment in PD-L1 combination studies. Clinical trial information: NCT02549937.