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

NCT06791512 | Recruiting Phase 3

• 1 other identifier: E2024365
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Colorectal cancer; pMMR/MSS; Neoadjuvant Therapy; PD-1 monoclonal antibody; mFOLFOX6

Outcome Measures

Primary Outcomes (1)

• 3 years DFS Rate

  3 years Disease Free Survival Rate

  3 years

Secondary Outcomes (6)

• pCR rate

  1 year

• MPR rate

  1 year

• Toxicities Associated with Neoadjuvant Therapy

  1 year

• R0 resection rate

  1 year

• Down-stage rate

  1 year

Study Arms (2)

Neoadjuvant therapy of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody

EXPERIMENTAL

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

Neoadjuvant therapy of mFOLFOX6

ACTIVE COMPARATOR

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

Interventions

mFOLFOX6 DRUG

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.

Also known as: mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody

Neoadjuvant therapy of mFOLFOX6

mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody DRUG

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.

Also known as: mFOLFOX6

Neoadjuvant therapy of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the colon or upper rectum.
• 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.
• 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).
• 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.
• No symptoms of intestinal obstruction, or obstruction successfully relieved by proximal colostomy.
• No history of colorectal surgery.
• No prior chemotherapy or radiotherapy.
• 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.
• Endocrine therapy history: Not restricted.
• Signed informed consent obtained.

You may not qualify if:

• 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.
• Severe hypertension that is not well controlled by medication.
• History of HIV infection or active chronic Hepatitis B or C (with high viral DNA load).
• Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year prior to trial screening.
• Other active severe infections as defined by NCI-CTCAE v5.0.
• Evidence of distant metastasis beyond the pelvic region.
• Blood dyscrasias or organ dysfunction.
• History of pelvic or abdominal radiotherapy.
• Multiple colorectal cancer or multiple primary tumors.
• Epilepsy requiring treatment (e.g., steroids or anti-epileptic drugs).
• History of other malignancies within the past 5 years.
• History of drug abuse, or medical, psychological, or social conditions that could interfere with patient participation or the evaluation of study results.
• 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).
• Long-term use of immunosuppressants or systemic/topical corticosteroids (dose \>10 mg/day prednisolone or equivalent).
• Known or suspected allergy to any study-related drug.

Sponsors & Collaborators

• Jun Huang: lead

Study Sites (1)

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jun Huang, MD

  The Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Huang, MD

CONTACT

+8613926451242; huangj97@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 19, 2025
• First Posted: January 24, 2025
• Study Start: January 18, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)