514MO - The efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI as first-line (1L) treatment for metastatic colorectal cancer (mCRC)

Background

FOLFOXIRI plus bevacizumab is the standard 1L treatment for mCRC. While the benefit of immunotherapy in microsatellite stable (MSS) mCRC remains unclear. Ivonescimab is a tetrameric bispecific antibody targeting PD-1 and VEGF. Ligufalimab is a novel humanized IgG4 monoclonal antibody targeting CD47. This study aimed to evaluate the efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI in mCRC.

Methods

This was an open-label, multicenter, phase 2 randomized study. Untreated mCRC patients (pts) were randomly assigned (1:1) to receive FOLFOXIRI + ivonescimab (group A) or FOLFOXIRI + ivonescimab + ligufalimab (group B) for up to 8 cycles, followed by maintenance with 5-fluoruracil + ivonescimab with (group B) or without ligufalimab (group A). The primary endpoints were objective response rate (ORR) by RECIST v1.1 and safety.

Results

As of Feb 29, 2024, 40 pts with mCRC were enrolled and randomly assigned to group A (n=22) and group B (n=18), with a median age of 58.5 and 57.0 years, respectively. KRAS/BRAF was mutated in 11 (50%) pts in group A and 11 (61.1%) pts in group B. All the pts were MSS except one pt whose status was unknown. The median follow-up was 9 months in group A and 9.6 months in group B. One pt in group B had no post-baseline tumor assessment. The ORR was 81.8% (18/22) in group A and 88.2% (15/17) in group B. The disease control rate was 100% in both groups. The median progression-free survival (PFS) and overall survival were not mature. The PFS rate at 9 months was 81.4% (95% CI: 52.1%-93.7%) in group A and 86.2% (95% CI: 55%-96.4%) in group B. A total of 18 pts (81.8%) in group A and 18 pts (100%) in group B experienced at least one treatment-related adverse event (TRAE); only 1 (5.6%) pt in group B discontinued treatment due to TRAE. Twelve (54.5%) pts in group A and 8 (44.4%) in group B had grade ≥3 TRAEs. The most common grade 3/4 TRAEs with a frequency ≥10% included decreased neutrophil count, decreased white blood cell count, diarrhea, and hypertension.

Conclusions

Ivonescimab with or without ligufalimab in combination with FOLFOXIRI showed promising efficacy and tolerable safety as 1L treatment in pts with mCRC.

Clinical trial identification

NCT05382442.

Editorial acknowledgement

Legal entity responsible for the study

Akeso Biopharma, Inc.

Funding

Akeso Biopharma, Inc.

Disclosure

X. Yu: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc.. Z.M. Wang: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc.. B. Li: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc.. Y. Xia: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc.. All other authors have declared no conflicts of interest.