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

ConditionsColorectal Cancer (CRC)pMMR/MSS Adenocarcinoma of the Colon or Rectum
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-80
SponsorJun Huang

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

Treatment groups

166 Participants
are divided into 2 treatment groups
Group A: Neoadjuvant therapy of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibodyExperimental treatment 1 intervention
Group B: Neoadjuvant therapy of mFOLFOX6Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

3 years DFS Rate

3 years Disease Free Survival Rate

Time frame
3 years

Secondary outcomes

1

pCR rate

pathological complete response rate

Time frame
1 year
2

MPR rate

major pathologic response

Time frame
1 year
3

Toxicities Associated with Neoadjuvant Therapy

Incidence of adverse events related to neoadjuvant therapy as assessed by CTCAE v5.0

Time frame
1 year
4

R0 resection rate

R0 resection rate in participants

Time frame
1 year

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Jun Huang

Lead sponsor

Sixth Affiliated Hospital, Sun Yat-sen University

Sponsor institution

Source ClinicalTrials.gov
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