A phase II study to evaluate the efficacy and safety of fruquintinib combined with tislelizumab and hepatic artery infusion chemotherapy (HAIC) for advanced colorectal cancer liver metastases: An updated analysis of survival.

3543 Background: We previously have showed that fruquintinib combined with tislelizumab and HAIC had an ORR benefit (25.71%) consisting of 1 CR and 8 PR in advanced colorectal cancer liver metastases (CRLM) patients (pts) who had failed to standard therapy in this single-arm, open-label, single center phase II study (NCT05435313). Here, we aim to update the survival results. Methods: We enrolled CRLM pts who had failed to standard therapy. Eligible pts received fruquintinib (3mg, qd, po, D2-21, Q3W), combined with tislelizumab (200mg, ivgtt, D2,Q3W) and HAIC (TOMOX: raltitrexed 2mg/m 2 , D1, oxaliplatin 85mg/m 2 , D1, Q3W; or TOMIRI: raltitrexed 2mg/m 2 , D1, irinotecan 120mg/m 2 , D1, Q3W) for 4-6 cycles, followed by maintenance therapy with fruquintinib and tislelizumab until disease progression, death or unacceptable toxicity. The primary endpoint was ORR. The secondary endpoints included DCR, PFS, 6mo-PFS rate, OS and safety. In addition, subgroup analysis of ORR and PFS according to primary tumor site, RAS/BRAF status and history of bevacizumab (bev) were performed. Results: Between July 17, 2022 and June 15, 2023, 39 pts (median age, 59 years range: 35--73, 25 64.1% male, 7 17.95% right-sided tumor, 38 97.44% MSS, 20 51.28% RAS/BRAF mutation) were enrolled. Among them, 23 (58.97%) pts had previously received bev. As of December 31, 2023, there were 4 pts drop out and 35 pts with MSS were included in the efficacy analysis. At a median follow-up of 12.52 mo, the median PFS was 7.43 mo (95%CI, 5.36-9.82) and 6mo-PFS rate was 60%, the median OS was 15.51mo (95%CI, 10.84-NA) and 1 year-OS rate was 61%. In the subgroup analysis, the median PFS was significantly longer with right-sided tumor pts than left-sided tumor pts (13.31 vs 6.90 mo, HR, 0.121 95%CI, 0.046-0.320, p= 0.0062). Compared with pts who received bev in prior therapy, the median PFS of pts without bev was significantly improved (5.16 vs 8.31 mo, HR, 0.358 95%CI, 0.133-0.965, p=0.0361). Favorable PFS was observed in RAS/BRAF mutation pts compared with RAS/BRAF wide-type pts (8.18 vs 7.43 mo). The results of PFS subgroups were consistent with ORR subgroup results (right-sided vs left-sided: 42.86% vs 21.43%, with bev vs without bev: 10% vs 46.67%) which was previously reported. Compared with safety profile reported previously, no additional safety signals were observed. Conclusions: The updated data on the survival analysis revealed that fruquintinib combined with tislelizumab and HAIC had a survival benefit in CRLM pts with MSS who had failed to standard therapy, especially for right-sided tumor pts. Based on these results, another study is ongoing to explore the efficacy for MSS CRLM pts with two cohorts (cohort 1: right-sided tumor, cohort 2: left-sided tumor), and the results will be presented in the future. Clinical trial information: NCT05435313 .