Genotype-directed targeted therapy combined with HAIC and tislelizumab for microsatellite-stable colorectal cancer liver metastasis refractory to multiple-line systemic therapy (proof-of-concept SALVLIVE trial): An interim analysis.

Abstract

e15545 Background: The prognosis of microsatellite-stable (MSS) colorectal cancer liver metastasis (CRCLM) refractory to systemic therapy is dismal. Previous studies had showed the efficacy of hepatic arterial infusion chemotherapy (HAIC) for CRCLM. Thus, this trial assesses the proof-of-concept for combining genotype-directed targeted therapy, HAIC, and tislelizumab in heavily pretreated MSS-CRCLM. Methods: This prospective, open-label, single-center trial screened participants with MSS-CRCLM refractory to multiple-line systemic therapy. Participants received the combination therapy of HAIC, tislelizumab (200 mg intravenously before HAIC on day 1), and targeted therapy every 4 weeks. The targeted therapy was determined based on genotype: fruquintinib (3 mg/day on day 3 - 21) was used for KRAS/NRAS/BRAF/EGFR mutation-type or failure of cetuximab in past 3 months (Arm A), while cetuximab (500 mg/m 2 ) was used for KRAS/NRAS/BRAF/EGFR wile-type without the usage of cetuximab in past 3 months (Arm B). The primary endpoint was 6-month progression-free survival (PFS) rate. PFS, overall survival (OS), hepatic PFS (HPFS), objective response rate (ORR), disease control rate (DCR), and safety were also investigated. Results: Between February 2024 and October 2025, 59 participants (57.4 ± 9.2 years old, 39 male) were enrolled (37 in Arm A and 22 in Arm B). The 6-months PFS rate was 51.7% (Arm A: 39.7%, Arm B: 67.5%), with the median PFS of 6.1 months (95% confidence interval [CI]: 5.524 – 6.676). The median OS and HPFS were 17 (95% CI: 14.969 – 19.031) and 8.1 months (95% CI: 7.402 – 8.798), respectively. The ORR was 64.4% (mRECIST)/47.5% (RECIST1.1), with a DCR of 96.6%. The incidence of ≥ grade 3 adverse events (AEs) was 25.4%. The most common ≥ grade 3 AEs in Arm A was elevated alanine transaminase (3/37, 8.1%), hyperbilirubinemia (3/37, 8.1%), and abdominal pain (3/37, 8.1%); and the most common ≥ grade 3 AEs in Arm B was thrombocytopenia (2/22, 9.1%). Conclusions: These interim results provided clinical proof-of-concept for the genotype-directed combination of targeted therapy, HAIC, and tislelizumab as a viable salvage strategy for heavily pretreated MSS-CRCLM. The trial is still ongoing, and the results will be updated in the future. Clinical trial information: NCT06199232 . Endpoints in Arm A and Arm B. Total Arm AFruq+HAIC+Tisl Arm BCet+HAIC+Tisl 6-month PFS rate 51.7% 39.7% 67.5% PFS 6.1 months(95% CI: 5.524 – 6.676) 5.7 months (95% CI: 5.037 – 6.363) 7.4 months (95% CI: 4.799 – 10.001) OS 17 months(95% CI: 14.969 – 19.031) 15.7 months (95% CI: 7.983 – 23.417) Not reach HPFS 8.1 months(95% CI: 7.402 – 8.798) 7.8 months (95% CI: 5.566 – 10.034) 8.2 months(95% CI: 7.094 – 9.306) ORR (mRECIST/RECIST1.1) 64.4% /47.5% 62.2% /37.8% 68.2% /63.6% DCR 96.6% 97.3% 95.5% Incidence of ≥ grade 3 AEs 25.4% 29.7% 18.2%