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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer (CRC); pMMR/MSS Adenocarcinoma of the Colon or Rectum
• Intervention / Treatment: Drug: mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody; Drug: mFOLFOX6

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).

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jun Huang, MD; Phone Number: +8613926451242; Email: huangj97@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • The Sixth Affiliated Hospital, Sun Yat-sen University
      • Contact: Jun Huang, MD; Phone Number: +8613926451242; Email: huangj97@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the colon or upper rectum.
2. Tumor biopsy immunohistochemical (IHC) identified pMMR, including all of the MSH1,MSH2,MSH6 and PMS2 protein expression and diagnosed as proficient mismatch repair(pMMR), or microsatellite stable (MSS) identified through next-generation sequencing or polymerase chain reaction.
3. Clinical staging of cT4NxM0, with or without positive mesorectal fascia (MRF), and with or without extramural vascular invasion (EMVI); imaging confirms that the lower margin of the tumor is located above the peritoneal reflection (colon or upper rectum).
4. Staging method: All patients must undergo chest, abdominal, and pelvic contrast-enhanced CT, rectal palpation, and high-resolution MRI. Positive perienteric lymph nodes (LNs) are defined as LNs with a short diameter ≥10 mm or LNs exhibiting typical metastatic shape and MRI characteristics. When staging results are contradictory, clinical data must be re-evaluated and confirmed by the central evaluation group. Distant metastases must be excluded through chest and abdominal contrast-enhanced CT and pelvic contrast-enhanced MRI.
5. No symptoms of intestinal obstruction, or obstruction successfully relieved by proximal colostomy.
6. No history of colorectal surgery.
7. No prior chemotherapy or radiotherapy.
8. No history of biopharmaceutical treatments (e.g., monoclonal antibody ), immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies), or treatment with investigational drugs.
9. Endocrine therapy history: Not restricted.
10. Signed informed consent obtained.

Exclusion Criteria:

1. Arrhythmias requiring anti-arrhythmic treatment (except β-blockers or Digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the past 6 months), or congestive heart failure (CHF) > NYHA Class II.
2. Severe hypertension that is not well controlled by medication.
3. History of HIV infection or active chronic Hepatitis B or C (with high viral DNA load).
4. Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year prior to trial screening.
5. Other active severe infections as defined by NCI-CTCAE v5.0.
6. Evidence of distant metastasis beyond the pelvic region.
7. Blood dyscrasias or organ dysfunction.
8. History of pelvic or abdominal radiotherapy.
9. Multiple colorectal cancer or multiple primary tumors.
10. Epilepsy requiring treatment (e.g., steroids or anti-epileptic drugs).
11. History of other malignancies within the past 5 years.
12. History of drug abuse, or medical, psychological, or social conditions that could interfere with patient participation or the evaluation of study results.
13. Any active autoimmune disease or a history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators).
14. Administration of any live attenuated vaccine within 4 weeks prior to inclusion.
15. Long-term use of immunosuppressants or systemic/topical corticosteroids (dose >10 mg/day prednisolone or equivalent).
16. Known or suspected allergy to any study-related drug.
17. Any unstable condition that could compromise patient safety or compliance.
18. Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception.
19. Refusal to provide signed informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant therapy of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody; Participants will receive the first five doses of 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.	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.; Other Names: mFOLFOX6
Active Comparator: Neoadjuvant therapy of mFOLFOX6; Participants 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).	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.; Other Names: mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 years DFS Rate	3 years Disease Free Survival Rate	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 years OS Rate	3 years Overall Survival Rate	3 years
R0 resection rate	R0 resection rate in participants	1 year
pCR rate	pathological complete response rate	1 year
MPR rate	major pathologic response	1 year
Toxicities Associated with Neoadjuvant Therapy	Incidence of adverse events related to neoadjuvant therapy as assessed by CTCAE v5.0	1 year
Down-stage rate	Down-stage rate of pathological stage after surgery compared with clinical stage before neoadjuvant therapy	1 year

Collaborators and Investigators

• Sponsor: Jun Huang
• Investigators: Principal Investigator: Jun Huang, MD, The Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: January 19, 2025
• First Submitted That Met QC Criteria: January 19, 2025
• First Posted (Actual): January 24, 2025

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Colorectal cancer; Neoadjuvant Therapy; mFOLFOX6; PD-1 monoclonal antibody; pMMR/MSS
• 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; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: E2024365

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