NCT07021950

AK112 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI as Second-line Treatment of MSS/pMMR Metastatic Colorectal Cancer

Ivonescimab (AK112) Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI as Second-line Treatment of MSS/pMMR Metastatic Colorectal Cancer: a Randomized, Controlled, Multicenter Phase II Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is a multicenter, open-label phase II trial conducted to assess the safety and antitumor activity of Ivonescimab (AK112) plus FOLFIRI versus bevacizumab plus FOLFIRI as second-line treatment in subjects with MSS/pMMR metastatic colorectal cancer who have experienced intolerance to oxaliplatin-containing first-line therapy or disease progression, or recurrence within 6 months after oxaliplatin adjuvant therapy.

Detailed description

After obtaining informed consent, the experimental group receives AK112 at 20 mg/kg via intravenous infusion on day 1 of each cycle (Q2W) combined with FOLFIRI chemotherapy (Q2W), while the control group receives bevacizumab at 5 mg/kg via intravenous infusion on day 1 of each cycle (Q2W) in combination with FOLFIRI (Q2W). Treatment continues until disease progression, death, intolerable toxicity, withdrawal of consent, initiation of new antitumor therapy, or other protocol-specified reasons for discontinuation. The maximum treatment duration is 24 months.

Conditions

• Colorectal Cancer
• Ivonescimab

Interventions

Type	Name	Description
DRUG	AK112	AK112：20mg/kg，Q2W。Administered over 60 minutes (±10 minutes). For intolerable cases, infusion duration may extend up to 120 minutes. During treatment, dosing delays are allowed for up to 12 weeks (calculated from the last dose). AK112 may be resumed after 12 weeks under the following conditions: If treatment is paused due to glucocorticoid tapering for managing immune-related adverse events (irAEs);If treatment is paused due to adverse events unrelated or deemed unrelated to AK112; Resumption is permitted only if the investigator judges continued therapy beneficial, following discussion with relevant medical personnel.
DRUG	FOLFIRI	FOLFIRI：Irinotecan, 180 mg/m² IV over 30-90 minutes (Day 1); Leucovorin (LV), 400 mg/m² IV over 2 hours (Day 1); 5-FU, 400mg/m²IV Day1, then 1200 mg/(m².d) ×2 days (total 2400 mg/m² ,IV over 46-48 hours).Q2W.
DRUG	Bevacizumab	Bevacizumab：5 mg/kg，Q2W. The initial intravenous infusion should last approximately 90 minutes. If the first infusion is well tolerated, the duration of the second infusion can be reduced to approximately 60 minutes. Should the participant also tolerate the 60-minute infusion well, then all subsequent infusions may be administered over a period of approximately 30 minutes. Continuous monitoring for potential infusion-related reactions during the drip is required; if an infusion-related reaction occurs, the infusion rate should be promptly reduced or the infusion temporarily halted.

Timeline

• Start date: 2025-08-10
• Primary completion: 2027-10-31
• Completion: 2028-12-31
• First posted: 2025-06-15
• Last updated: 2025-06-15