NCT06791512

mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody Vs. mFOLFOX6 in Locally Advanced pMMR/MSS CRC

mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody Versus mFOLFOX6 as Neoadjuvant Therapy for Locally Advanced pMMR/MSS Colorectal Cancer: A Prospective, Multicenter, Randomized Phase III Study (BASKETIII)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 166 (estimated)
• Sponsor: Jun Huang · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Neoadjuvant immunotherapy has shown promising therapeutic effects in mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, for patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS) CRC, the efficacy of PD-1 monoclonal antibody remains limited. Enhancing the efficacy of immunotherapy in pMMR/MSS CRC has become a key area of exploration. Additionally, for locally advanced (cT4NxM0) CRC patients, achieving R0 resection poses a significant challenge. Failure to achieve R0 resection often results in recurrence, severely impacting patient survival outcomes. Our previous phase II clinical study (BASKET Ⅱ) demonstrated that the neoadjuvant regimen of mFOLFOX6 combined with Bevacizumab and PD-1 monoclonal antibody significantly enhanced the immunotherapy sensitivity of locally advanced pMMR/MSS CRC, leading to improved pathological complete response (pCR) rates and higher R0 resection rates. This prospective, multicenter, randomized phase III trial aims to evaluate whether the neoadjuvant regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody can further improve pCR rate, enhance survival outcomes, and maintain an acceptable safety profile compared to mFOLFOX6 alone in pMMR/MSS locally advanced CRC patients.

Detailed description

This clinical trial is an open-label, prospective, multicenter, randomized phase III study. The aims of this study are to evaluate whether the the neoadjuvant regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody can improve the pathological complete response (pCR) rate, enhance survival outcomes, and maintain manageable toxicity compared to mFOLFOX6 alone in patients with locally advanced pMMR/MSS CRC. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group or the control group. Participants in the experimental group will receive the neoadjuvant therapy regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody. And the first five doses will receive the neoadjuvant therapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and a 48-hour continuous infusion of 5-fluorouracil 2400 mg/m2) combined with sintilimab (200 mg, intravenous) and Bevacizumab (5 mg/kg, intravenous). The sixth dose will consist of the same regimen of mFOLFOX6 and PD-1 monoclonal antibody, but not plus bevacizumab, in order to allow sufficient withdrawal time of Bevacizumab for surgery. Participants in the control group will receive the neoadjuvant therapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and a 48-hour continuous infusion of 5-fluorouracil 2400 mg/m2) alone. Subjects in both the experimental and control groups will undergo radical surgical treatment after completing the neoadjuvant therapy. Those achieving pCR based on postoperative pathology will be regularly followed up according to the follow-up protocol. Participants who do not achieve pCR will receive six cycles of adjuvant therapy after surgery, followed by regular follow-up assessments as outlined in the protocol after completing the final cycle of adjuvant therapy. The primary outcome of this study is to evaluate the 3-year disease-free survival (DFS). Secondary objectives include the pCR rate, major pathological response (MPR) rate, neoadjuvant therapy-related toxicities, R0 resection rate, tumor downstaging rate, and overall survival (OS).

Conditions

• Colorectal Cancer (CRC)
• pMMR/MSS Adenocarcinoma of the Colon or Rectum

Interventions

Type	Name	Description
DRUG	mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody	Participants in the experimental group will receive the neoadjuvant therapy regimen of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody. And the first five doses received the neoadjuvant therapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and 5-fluorouracil 2400 mg/m2 continuous pumping for 48 hours) combined with sintilimab (200 mg, intravenous) and Bevacizumab (5 mg/kg, intravenous), and the sixth dose received the same regimen of mFOLFOX6 and PD-1 monoclonal antibody but not plus bevacizumab, in order to allow sufficient withdrawal time of Bevacizumab for surgery.
DRUG	mFOLFOX6	Participants in the control group will receive the neoadjuvant therapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and 5-fluorouracil 2400 mg/m2 continuous pumping for 48 hours) alone.

Timeline

• Start date: 2025-01-18
• Primary completion: 2030-12-31
• Completion: 2031-12-31
• First posted: 2025-01-24
• Last updated: 2025-12-24

Locations

1 site across 1 country: China