A phase II trial of fruquintinib combined with cadonilimab in refractory MSS/pMMR colorectal cancer with pulmonary metastases.

3552 Background: Immunotherapy for metastatic colorectal cancer (mCRC) with microsatellite stable/proficient mismatch repair (MSS/pMMR) remains limited. Emerging evidence suggests that the combination of antiangiogenic agents and immune checkpoint inhibitors (ICIs) exhibits synergistic antitumor effects in refractory MSS/pMMR mCRC, particularly among patients (pts) with isolated lung metastases. This open-label, single-arm, phase II trial aims to evaluate the efficacy and safety of fruquintinib plus cadonilimab in pts with MSS/pMMR mCRC who progressed after at least two prior lines of therapy. Methods: Patients aged≥18 years, with pathologically confirmed MSS/pMMR mCRC presenting pulmonary metastases and no liver metastases, and who had experienced failure of at least second-line therapy were enrolled. Eligible patients received oral fruquintinib (3 mg once daily) plus intravenous cadonilimab (6 mg/kg every two weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Tumor assessments were performed every 8 weeks. The primary endpoint was objective response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Results: From February 2024 to June 2025, 37 pts were enrolled [median age 61 years, 68% male, 89% ECOG 0-1, 62% RAS mutant, 30% 3L+, 73% prior bevacizumab, 3 pts prior immunotherapy]. The ORR was 31.4%, and the DCR was 71.4%. Median PFS was 6.1 months (95%CI: 4.8-7.5), while OS data remain immature. Moreover, the patients with a history of liver metastases showed a trend toward shorter PFS compared to those without (4.0 vs. 6.9 months; P = 0.194). The most common treatment-related adverse events (AEs) were hypothyroidism (43%), elevated ALT/AST (27%), hypertension (24%), diarrhea (24%), thrombocytopenia (19%), hand-foot syndrome (16%), and rash (16%). Grade ≥3 treatment-related AEs occurred in 10 (27%) pts. Serious adverse events (SAEs) were reported in 5 pts, with no grade 4 or 5 SAEs observed. Conclusions: The combination of fruquintinib and cadonilimab demonstrated promising clinical activity and a manageable safety profile in patients with refractory MSS/pMMR mCRC. Clinical trial information: ChiCTR2400079429.