637P 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 (CRLM)

Metastases to the liver remain the primary driver of disease-specific mortality for colorectal cancer (CRC). The FRESCO study has shown that fruquintinib significantly prolongs the survival of CRLM patients (pts). Meanwhile the combination of fruquintinib and PD-1 inhibitors has shown promising efficacy in advanced CRC. HAIC is an unique and effective option for CRLM pts. So we carried out a study to assess the efficacy and safety of fruquintinib combined with tislelizumab and HAIC for advanced CRLM pts. We enrolled CRLM pts who had failed standard therapy in this phase II study (NCT05435313). Eligible pts received fruquintinib (3mg, qd, po, D2-21, Q3W) in combination with tislelizumab (200mg, ivgtt, D2,Q3W) and HAIC (TOMOX: raltitrexed 2mg/m2, D1, oxaliplatin 85mg/m2, D1, Q3W; or TOMIRI: raltitrexed 2mg/m2, D1, irinotecan 120mg/m2, 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 were DCR, PFS, 6mo-PFS%, OS and safety. Between July 17, 2022 and April 27, 2022, 38 pts were enrolled. Median age was 59 (range: 35-73) years and 24 were male, MSS accounted for 37 pts and 18 pts harboring RAS mutation. 22 and 4 pts had previously received bevacizumab and regorafenib, respectively. At data cut off, 29 pts with MSS had efficacy evaluation data, the combination therapy provided an ORR of 27.59% (1 CR, 7 PR) and a DCR of 93.10% (19 SD). ORRs of RAS mutation and wild type were 14.29% (2/14) and 40% (4/10), respectively. 19 (65.52%) of 29 pts showed evidence of a reduction in tumour volume. Neither median PFS nor median OS were reached. TEAEs were mainly grade 1/2, Grade 3/4 TEAEs occurred in 5 pts, including hypertension, hand-foot-skin reactions, GGT increased, neutrophil decreased and AST increased. No treatment related death. Fruquintinib combined with tislelizumab and HAIC showed promising efficacy and acceptable safety for CRLM pts who had failed standard therapy in this interim analysis. Updated data will be presented in the future.