The CONVERGE study: A phase II, single-arm trial of adebelimab combined with targeted therapy and liposomal irinotecan-based chemotherapy for conversion surgery in unresectable MSS colorectal cancer liver metastases.

Abstract

3604 Background: Liver metastasis is a key poor prognostic factor for colorectal cancer (CRC). Microsatellite stable (MSS) CRC predominates and is poorly responsive to single-agent immunotherapy. Only 10%–20% of patients with initially unresectable MSS colorectal cancer liver metastases (CRLM) are eligible for upfront curative resection, and conventional chemo-targeted therapy yields a conversion resection rate of merely 15%–30%. This phase II study evaluated the efficacy and safety of adebelimab (a PD-L1 inhibitor) plus molecularly stratified targeted therapy and liposomal irinotecan-based chemotherapy for unresectable MSS CRLM, focusing on hepatic metastatic lesion control (ChiCTR2600117031). Methods: This single-center, open-label phase II trial enrolled 45 patients with unresectable MSS CRLM (ECOG PS 0-1, no prior systemic anti-tumor therapy). Patients received adebelimab (1200mg IV, Q2W) + stratified targeted therapy (cetuximab for RAS/BRAF wild-type left-sided tumors; bevacizumab otherwise) + liposomal irinotecan-based chemotherapy (Q2W) for up to 12 cycles. Primary endpoint: conversion-to-resection rate. Secondary endpoints: ORR, DCR, R0 resection rate, hepatic metastasis pathological response, and safety (NCI-CTCAE v5.0). Efficacy was assessed per RECIST v1.1. Results: As of January 20, 2026, 42 patients were included in baseline analysis (median age 57.6±11.1 years, 64.3% male; mean hepatic metastasis diameter 37.21±19.00 mm, max 82.79 mm). Among 35 efficacy-evaluable patients, ORR was 45.7% (95% CI: 28.8%–63.4%) and DCR was 88.6% (95% CI: 73.3%–96.8%). Fourteen patients underwent surgery (conversion rate 45.2%, 95% CI: 27.3%–60.0%), all completing simultaneous resection of hepatic metastases and primary tumors. Of these 14 patients, 5 (35.7%) achieved hepatic TRG 0 (complete pathological regression) and 12 (85.7%) achieved R0 resection (95% CI: 49.2%–95.3%). For safety, 95.2% (40/42) of patients had AEs. Common (≥10%) all-grade AEs were mainly hematological (leukopenia 23.8%, myelosuppression 21.4%). Grade 3 AEs were rare (predominantly leukopenia 14.3%), and no grade 4 AEs occurred. No any-grade immune-related AEs were reported. Conclusions: Adebelimab combined with molecularly stratified targeted therapy and liposomal irinotecan-based chemotherapy shows substantial efficacy and favorable safety for unresectable MSS CRLM, with excellent hepatic metastasis control. Its high conversion-to-resection rate and 35.7% hepatic TRG 0 rate confirm potential for deep pathological response. This regimen warrants further investigation as a promising conversion therapy for unresectable MSS CRLM. Genomic sequencing of successfully converted patients is ongoing to elucidate therapeutic mechanisms. Clinical trial information: ChiCTR2600117031.