NCT07383285

CAPOX and Bevacizumab With or Without Primary Tumor Radiotherapy and Iparomlimab and Tuvonralimab as First-line Treatment for RAS-Mutant/MSS Metastatic Rectal Cancer

CAPOX and Bevacizumab With or Without Primary Tumor Radiotherapy and Iparomlimab and Tuvonralimab as First-line Treatment for RAS-Mutant/MSS Metastatic Rectal Cancer: An Open-label, Randomized, Multi-center Phase II Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 106 (estimated)
• Sponsor: Peking University Cancer Hospital & Institute · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Research objective: To compare the efficacy and safety of Capox + Bev versus Capox + Bev combined with primary site radiotherapy + (Iparomlimab and Tuvonralimab) as the first-line treatment for RAS Mutation/pMMR metastatic rectal cancer patients. Study endpoint: Primary endpoint: 12-month progression-free survival rate (PFSR) Secondary endpoints: * The objective response rate (ORR) and disease control rate (DCR) as determined by the investigator according to the RECIST 1.1 standard, time to response (TTR), duration of response (DOR), progression-free survival (PFS), 6-month progression-free survival rate (PFSR), overall survival (OS); * The frequency and severity of adverse events (AEs) during treatment (NCI CTCAE 5.0). This study will enroll 106 patients (stratification factors: presence or absence of liver metastasis; whether NED could be achieved). They were randomly assigned in a 1:1 ratio to: The treatment group: Capox + Bev combined with primary site radiotherapy and (Iparomlimab and Tuvonralimab), administered every 3 weeks (Q3w), up to a maximum of 8 cycles, followed by a maintenance treatment stage of Capecitabine + Bev + (Iparomlimab and Tuvonralimab), administered every 3 weeks (Q3w). The control group: Capox + Bev, administered every 3 weeks (Q3w), up to a maximum of 8 cycles, followed by a maintenance treatment stage of Capecitabine + Bev, administered every 3 weeks (Q3w).

Detailed description

This study is an open-label, randomized controlled, multicenter phase II clinical trial, aiming to evaluate the efficacy and safety of the Capox + Bev combination (with or without concurrent primary lesion radiotherapy + (Iparomlimab and Tuvonralimab) as the first-line treatment for patients with RAS mutation/pMMR metastatic rectal cancer. This study will enroll 106 patients, (stratification factors: presence or absence of liver metastasis; whether NED could be achieved) and was randomly assigned in a 1:1 ratio to: The treatment group: Capox + Bev combined with primary lesion radiotherapy and (Iparomlimab and Tuvonralimab), administered once every 3 weeks (Q3w), for a maximum of 8 cycles, followed by a maintenance treatment stage of Capecitabine + Bev + (Iparomlimab and Tuvonralimab), administered once every 3 weeks (Q3w). The control group: Capox + Bev, administered once every 3 weeks (Q3w), for a maximum of 8 cycles, followed by a maintenance treatment stage of Capecitabine + Bev, administered once every 3 weeks (Q3w). Treatment plan The experimental group will receive Capox + Bev combined with primary lesion radiotherapy and (Iparomlimab and Tuvonralimab): Oxaliplatin 130mg/m2 on day 1, Capecitabine 1000mg/m2 twice daily from day 1 to day 14, Bevacizumab 7.5mg/kg on day 1, (Iparomlimab and Tuvonralimab) 5mg/kg on day 1, repeated every 3 weeks, up to a maximum of 8 cycles. On the third cycle, primary lesion radiotherapy is conducted simultaneously, with the specific range and dose of 95% PGTV (rectal primary lesion) 25Gy/5 fractions \[Before and after radiotherapy, the chemotherapy and Bevacizumab can be adjusted (stopped or reduced) according to the specific patient's adverse reactions\]. Then enter the Capecitabine + Bev + (Iparomlimab and Tuvonralimab) maintenance treatment: Capecitabine 1000mg/m2 twice daily from day 1 to day 14, Bevacizumab 7.5mg/kg on day 1, (Iparomlimab and Tuvonralimab) 5mg/kg on day 1, repeated every 3 weeks. Until disease progression, occurrence of intolerable toxicity, acceptance of new anti-tumor treatment, withdrawal of informed consent, loss to follow-up, death, or other researchers determine that treatment should be stopped, whichever occurs first. If during the treatment process, one drug is discontinued for any reason, other drugs can continue to be used. The control group will receive Capox + Bev: Oxaliplatin 130mg/m2 on day 1, Capecitabine 1000mg/m2 twice daily from day 1 to day 14, Bevacizumab 7.5mg/kg on day 1, repeated every 3 weeks, up to a maximum of 8 cycles. Then enter the Capecitabine + Bev maintenance treatment: Capecitabine 1000mg/m2 twice daily from day 1 to day 14, Bevacizumab 7.5mg/kg on day 1, repeated every 3 weeks. Until disease progression, occurrence of intolerable toxicity, acceptance of new anti-tumor treatment, withdrawal of informed consent, loss to follow-up, death, or other researchers determine that treatment should be stopped, whichever occurs first. If during the treatment process, one drug is discontinued for any reason, other drugs can continue to be used.

Conditions

• Rectal Neoplasms Malignant

Interventions

Type	Name	Description
DRUG	Iparomlimab and Tuvonralimab	(Experimental group) PD-1/CTLA-4 Antibody
RADIATION	Radiotherapy to the primary site	(Experimental group) Radiotherapy to the primary site of rectal
DRUG	Capecitabine	(both groups)
DRUG	Bevacizumab	(both groups)
DRUG	Oxaliplatin injection	(both groups)

Timeline

• Start date: 2026-02-01
• Primary completion: 2029-12-31
• Completion: 2029-12-31
• First posted: 2026-02-03
• Last updated: 2026-02-03