Abstract 41P
Background
Treatment options for patients (pts) with RAS/BRAF MT MSS mCRC are limited. Surufatinib (S, a small-molecule inhibitor targeting VEGFR-1/2/3, FGFR-1 and CSF-1R) plus toripalimab (T, a PD-1 inhibitor) has shown synergistic anti-tumor effects in solid tumor pts. This single-arm, phase II study aims to investigate the efficacy and safety of S plus T and chemotherapy in RAS/BRAF MT MSS mCRC pts who received first-line therapy.
Methods
Eligible pts (pathologically confirmed mCRC with RAS/BRAF MT and MSS, failing first-line chemotherapy) were treated with S (250mg PO QD), T (3mg/kg, IV, D1) and standard 2nd-line chemotherapy every 2 weeks until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was ORR (per RECIST 1.1). Secondary endpoints included DCR, PFS, OS, and safety. Simon’s two-stage optimum design was employed, only ≥4 pts reached PR/CR in 19 pts (first stage), the study would be continued.
Results
At the cutoff date of Mar 15, 2024, 16 pts were enrolled [median age 60 years, 50% male, 75% ECOG PS 0, 56.25% with liver metastases (LMs), 68.75% prior bevacizumab]. ORR was 31.25% (5/16) and DCR was 93.75% (15/16). In pts without LMs, the ORR and DCR were 42.85% and 100.0%. Median PFS (mPFS) was 7.98 months (95%CI: 4.27-11.70), with bevacizumab-pretreated pts showing longer PFS (9.23 vs 5.75 months; p=0.91). OS data were immature. The most common treatment-related adverse events (any grade; grade 3/4) were neutropenia (56.5%; 52.2%), leukopenia (56.5%; 17.4%) and diarrhea (52.2%; 17.4%). Serious adverse events were reported in 5 pts with no grade 4 SAEs occurred.
Conclusions
Combination of surufatinib with toripalimab and chemotherapy showed promising antitumor activity and encouraging survival benefits with manageable safety in the second-line treatment for RAS/BRAF mutant microsatellite stable metastatic CRC. The results warrant further investigations in a large cohort.
Clinical trial identification
NCT04653480.
Legal entity responsible for the study
The First Affiliated Hospital, Zhejiang University School of Medicine.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.