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STS has a therapeutic challenge with limited preoperative treatment options. SUR, a kinase inhibitor targeting VEGFR 1, 2, 3, FGFR 1, and CSF-1R, has shown synergistic effects in combination with immunotherapy in previous studies. Furthermore, radiotherapy is reported to potentiate immunotherapy efficacy in "cold" tumors by inducing immunogenic death and remodeling the tumor microenvironment. This study aims to assess the combined preoperative efficacy and safety of RT, SUR, and SIN for STS. In this Ph Ib/II trial, up to 52 patients (pts) were planned to be enrolled. Pts underwent treatment with RT, SUR (250 mg, po, qd, every 21 days as a cycle), and SIN (200 mg, i.v., d1, q3w) for 6 cycles before surgery. Primary endpoint was objective response rate (ORR) according to RECIST 1.1 with secondary endpoints including the rate of pathological complete response (pCR) and near pCR (defined as < 10% viable tumor cells), progression free survival (PFS), overall survival (OS) and safety. The Ph Ib (3+3 design) assessed SUR's recommended phase 2 dose (RP2D), while Ph II focused on efficacy and safety. As of Dec., 2023, 7 unresectable STS (1 trunk STS and 6 limbs STS) pts were enrolled. The median age was 57 years (range 21-71). 6/7 (86%) was histological grade 3. Among the 7 pts, 6 (86%) pts underwent previous surgery and 5 (71%) pts received prior chemotherapy. One DLT (grade 3 increased bilirubin) was observed in 6 pts receiving SUR (250 mg, qd) in combination with SIN (200 mg, d1,q3w), and then the RP2D was confirmed. The most common TRAEs were increased blood bilirubin in 3/7 pts (43%) and diarrhea in 1/7 pts (14%). For the 6 evaluable pts, 3 achieved partial response and 2 had stable disease with an ORR of 50% (3/6) and a DCR of 83% (5/6). 5 pts underwent surgery with a 100% (5/5) rate of R0 resection, and all achieved limb preservation with no serious wound complications. The rate of pCR and near pCR reached 40% (2/5) with 1 pCR and 1 near pCR. Median PFS and OS had not yet reached. The combination of radiotherapy, SUR, and SIN showed a potential efficacy and tolerable toxicity in high-risk localized limbs and trunk STS. The trial is still ongoing.
Wang et al. (Fri,) studied this question.