1740P - Surufatinib combined with gemcitabine in soft tissue sarcoma (STS) patients failed with anthracyclines chemotherapy or monotherapy post-anlotinib progression: A multi-center, phase II trial

Background

Surufatinib (S), a novel small-molecule inhibitor targeting VEGFR-1, 2, 3, FGFR-1 and CSF-1R, has showed promising efficacy in recurrent STS patients (pts). Herein, we explored the efficacy and safety of S plus gemcitabine in STS pts progressed on first-line anthracyclines chemotherapy or anlotinib, an anti-angiogenic tyrosine kinase inhibitor (TKI).

Methods

In this multi-center, phase II study (ChiCTR2100053490), two cohorts were established. Eligible pts with STS failed to first-line anthracyclines chemotherapy were enrolled in cohort 1 and received S (250 mg, qd, po, q3w) plus gemcitabine (1000 mg/m², iv, d1, d8, q3w). Pts failed with anlotinib were assigned to cohort 2 and received S (300 mg, qd, po, q4w). Primary endpoint was PFS. Secondary endpoints included 8-week PFR (cohort 2 only), ORR, DCR, OS and safety.

Results

Up to 15 Apr, 2024, 17 pts were included in cohort 1 [median age 59 years, female 70.6%, leiomyosarcoma (LMS) 52.9%, lung metastases 64.7%]. In cohort 2, 8 patients were enrolled (median age 51.5 years, female 50%, 62.5% pts failed with at least 3 lines of previous therapies). In cohort 1, all 17 pts were evaluable, with an ORR of 17.65% and DCR of 82.35%. Median PFS (mPFS) was 4.37 months, with pts with lung metastases showing longer mPFS (11.66 vs 3.70 months, p=0.3213). mPFS in 9 LMS pts was 5.65 months with an ORR of 22.2%. In cohorts 2, 8 pts were evaluable, with mPFS of 3.25 months, and an 8-week PFR of 87.5%. In subgroup analysis, mPFS of pts received S as less than 4 lines of therapy was 3.61 months. The most common treatment-emergent adverse events (total; grade ≥3) in cohort 1 included hypothyroidism (29.4%; 0), proteinuria (17.6%; 5.9%), and neutrophil count decreased (17.6%; 5.9%); in cohort 2 were diarrhea (37.5%; 0), urinary tract infection (25.0%; 0), hypertension (12.5%; 12.5%).

Conclusions

Surufatinib combined with gemcitabine showed encouraging anti-tumor activity in STS pts failed in first-line standard chemotherapy, especially for pts with lung metastases. Additionally, surufatinib monotherapy also exhibited promising efficacy in pts previously treated with anti-angiogenic TKIs.

Clinical trial identification

ChiCTR2100053490.

Editorial acknowledgement

Funding

Hutchison Medi Pharma.

Disclosure

All authors have declared no conflicts of interest.