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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: Iparomlimab and tuvonralimab

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liangjun Zhu; Phone Number: 13505199123; Email: zhulj98@foxmail.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Cancer Hospital
      • Contact: Liangjun Zhu; Phone Number: 13505199123; Email: zhulj98@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

  1. White blood cell count ≥3.5×10⁹/L
  2. Absolute neutrophil count ≥1.5×10⁹/L
  3. Hemoglobin ≥100 g/L
  4. Platelets ≥80×10⁹/L
  5. Serum liver enzymes ≤2.5× upper limit of normal (ULN) in patients without liver metastases
  6. Serum liver enzymes ≤5× ULN in patients with liver metastases
  7. Serum bilirubin ≤1.5× ULN
  8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: QL1706+ bevacizumab+chemotherapy; The study consists of a 6-cycle induction treatment phase and a maintenance treatment phase. During the induction phase, patients receive iparomlimab and tuvonralimab combined with bevacizumab and chemotherapy. During the maintenance phase, patients receive iparomlimab and tuvonralimab combined with bevacizumab and capecitabine until disease progression or intolerable toxicity.

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. Patients with CR/PR/NED or SD are allowed to receive maintenance therapy until disease progression or intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Objective Response Rate（ORR）	CR+PR	From enrollment to the end of treatment at 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Progression-Free Survival（PFS）	The time from the start of treatment in cancer patients to the observation of disease progression or death from any cause	From enrollment to the end of treatment at 18 months
Investigator-assessed Duration of Response（DoR）	The time from the first assessment of complete response or partial response to the first assessment of tumor progression or death from any cause	From enrollment to the end of treatment at 18 months
Overall Survival（OS）	Time from enrollment to death from any cause	From enrollment to the end of treatment at 36 months
AE	safety	From enrollment to the end of treatment at 12 weeks

Collaborators and Investigators

• Sponsor: Jiangsu Cancer Institute & Hospital
• Investigators: Principal Investigator: Liangjun Zhu, Dr, Jiangu Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: bevacizumab; Combination therapy; mCRC; QL1706; Alternating chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: KY-2025-177

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No