KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy and safety of surufatinib plus toripalimab and chemo in pts with RAS/BRAF mutant MSS mCRC.
- The primary endpoint was to determine ORR.
- Researchers noticed promising antitumor activity, survival benefits, and manageable safety, warranting further investigation in a larger cohort.
Treatment options for patients (pts) with RAS/BRAF mutant (MT) microsatellite stable (MSS) metastatic colorectal cancer (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.
In this single-arm phase II study, Yi Zheng and the team aimed to aims to investigate the efficacy and safety of S plus T and chemotherapy (chemo) in RAS/BRAF MT MSS mCRC pts who received first-line (1L) therapy.
They performed an inclusive analysis on eligible pts (pathologically confirmed mCRC with RAS/BRAF MT and MSS, failing 1L chemo) treated with S (250 mg PO QD), T (3 mg/kg, IV, D1) and standard second-line (2L) chemo 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 2-stage optimum design was employed, and only if ≥4 pts reached PR/CR in 19 pts (1 stage), the study would be continued.
About 16 pts were enrolled [median age 60 years, 50% male, 75% ECOG PS 0, 56.25% with liver metastases (LMs), 68.75% prior bevacizumab] on the date of Mar 15, 2024. 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.
The study concluded that the combination of surufatinib with toripalimab and chemo showed promising antitumor activity and encouraging survival benefits with manageable safety in the (2L) treatment for RAS/BRAF mutant MSS mCRC. The results warrant further investigations in a large cohort.
The trial was sponsored by the Zhejiang University.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trial: https://clinicaltrials.gov/study/NCT04653480
Zheng Y, Zhang H, Liu L, et al. (2024). “Surufatinib plus toripalimab and chemotherapy for second-line treatment of RAS/BRAF mutant (MT) microsatellite stable (MSS) metastatic colorectal cancer (mCRC): A single-arm, phase II study (APHRODITE).” Presented at ESMO-GI 2024 (Abstract 41P).
