A Clinical Study of Iparomlimab and Tuvonralimab Combined With Bevacizumab and Alternating Triweekly CAPOX/mCAPIRI Regimen as First-line Treatment for Unresectable Advanced Colorectal Cancer

Official title

A Prospective, Single-arm, Multicenter Phase II Clinical Study of Iparomlimab and Tuvonralimab Combined With Bevacizumab and Alternating Triweekly CAPOX/mCAPIRI Regimen as First-line Treatment for Unresectable Advanced Colorectal Cancer

Overview

This study is a prospective, single-arm, multicenter exploratory clinical study aimed at evaluating the efficacy and safety of iparomlimab and tuvonralimab combined with bevacizumab and alternating triweekly CAPOX/mCAPIRI regimen as first-line treatment for unresectable advanced colorectal cancer. The study plans to enroll 70 patients with unresectable advanced metastatic colorectal cancer. After evaluation and confirmation of meeting enrollment criteria, patients will receive treatment with iparomlimab and tuvonralimab combined with bevacizumab and alternating triweekly CAPOX/mCAPIRI regimen. The primary endpoint of the study is ORR, and secondary endpoints include PFS, DoR, OS, and safety.

Interventions

• Drug Iparomlimab and tuvonralimab
  Induction Phase: Iparomlimab and tuvonralimab (5 mg/kg, Q3W, D1) + bevacizumab (7.5 mg/kg, Q3W, D1) + CAPOX regimen (oxaliplatin 130 mg/m², Q3W, D1; capecitabine 1,000 mg/m², BID, D1-14, Q3W) / mCAPIRI (irinotecan 180 mg/m², Q3W, D1; capecitabine 800 mg/m², BID, D1-14, Q3W) alternating every 42 days, assessed every 6 weeks, for a maximum of 6 cycles. Maintenance Phase: Iparomlimab and tuvonralimab 5 mg/kg, Q3W, D1 + bevacizumab 7.5 mg/kg, Q3W, D1 + capecitabine 800-1,000 mg/m², BID, D1, Q3W. Pa

Primary outcome measures

• Investigator-assessed Objective Response Rate（ORR） [Time frame: From enrollment to the end of treatment at 18 months]

Secondary outcome measures (4)

• Investigator-assessed Progression-Free Survival（PFS） [Time frame: From enrollment to the end of treatment at 18 months]
• Investigator-assessed Duration of Response（DoR） [Time frame: From enrollment to the end of treatment at 18 months]
• Overall Survival（OS） [Time frame: From enrollment to the end of treatment at 36 months]
• AE [Time frame: From enrollment to the end of treatment at 12 weeks]

Eligibility criteria

Inclusion criteria

• 1\. Age 18-75 years;
• 2\. Patients with histologically or cytologically confirmed unresectable, advanced colorectal cancer;
• 3\. No prior systemic treatment;
• 4\. ECOG PS score ≤2;
• 5\. Expected survival ≥3 months;
• 6\. MSS/MSI-L status;
• 7\. At least one evaluable lesion based on RECIST 1.1 criteria;
• 8\. No prior systemic chemotherapy or other systemic therapy, or only received adjuvant chemotherapy with disease progression or recurrence within 6 months after completion of treatment;
• 9\. Adequate organ function reserve, with specific hepatic, renal, and hematologic parameters as follows:

• White blood cell count ≥3.5×10⁹/L
• Absolute neutrophil count ≥1.5×10⁹/L
• Hemoglobin ≥100 g/L
• Platelets ≥80×10⁹/L
• Serum liver enzymes ≤2.5× upper limit of normal (ULN) in patients without liver metastases
• Serum liver enzymes ≤5× ULN in patients with liver metastases
• Serum bilirubin ≤1.5× ULN
• Serum creatinine ≤1.5× ULN
• 10\. No history of other malignancies;
• 11\. Voluntary participation in this study with signed informed consent.

Exclusion criteria

• 1\. Prior hypersensitivity to any of the study drugs;
• 2\. Active or known or suspected autoimmune disease requiring systemic treatment, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring bronchodilator intervention;
• 3\. Presence of non-measurable lesions (e.g., pleural effusion/ascites, carcinomatous lymphangitis, diffuse liver involvement, bone metastases);
• 4\. Pregnant or lactating women;
• 5\. Uncontrolled symptomatic brain metastases or psychiatric disorders preventing accurate expression of subjective symptoms;
• 6\. Vital organ function failure;
• 7\. Conditions affecting drug absorption/distribution/metabolism/excretion (e.g., seizures, central nervous system diseases, cognitive impairment due to psychiatric disorders, chronic diarrhea, cachexia, etc.);
• 8\. Patients with complete or incomplete intestinal obstruction;
• 9\. History of severe cardiac disease (including congestive heart failure, uncontrolled high-risk arrhythmia, angina requiring medication, definite valvular heart disease history, severe myocardial infarction, refractory hypertension);
• 10\. Active infection requiring systemic treatment;
• 11\. Known history of HIV infection;
• 12\. Known history of hepatitis B or active hepatitis C virus infection;
• 13\. Other conditions deemed unsuitable for enrollment by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Jiangsu Cancer Hospital — Nanjing

Identifiers

NCT: NCT07446387 · KY-2025-177

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗