Neoadjuvant mFOLFOX6 Chemotherapy Combined With Anti-PD-1 Therapy in MSS/pMMR Locally Advanced Rectal Cancer (FIRM02 Study)

NCT07381400 | Not Yet Recruiting Phase 2

• 1 other identifier: XHEC-C-2025-300-2
• Study Type: interventional
• Target: 128
• Locations: 0 countries
• Sites: N/A

Brief Summary

This multicenter, randomized controlled clinical trial (FIRM02 Study) aims to evaluate the effectiveness and safety of neoadjuvant mFOLFOX6 chemotherapy combined with PD-1 inhibitor (Serplulimab) in patients with MSS/pMMR locally advanced rectal cancer (LARC). A total of 128 patients with non-metastatic, untreated, locally advanced rectal cancer will be randomly assigned in a 1:1 ratio to either the experimental group (64 patients) or the control group (64 patients). The experimental group will receive 6 cycles of mFOLFOX6 chemotherapy combined with 3 mg/kg of Serplulimab every 2 weeks prior to surgery. The control group will receive 6 cycles of mFOLFOX6 chemotherapy alone. The primary endpoint is the pathological complete response (pCR), and secondary endpoints include major pathological response (MPR), tumor regression grade (TRG), overall response rate (ORR), and survival outcomes (DFS, RFS, and OS). Safety will be assessed based on adverse events and post-operative complications.

Conditions

Rectal Cancer

Keywords

rectal cancer; PD1 inhibitor; pMMR; microsatellite stable; neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response Rate (pCR)

  Day 7 after surgery

Secondary Outcomes (11)

• Major Pathological Response (MPR)

  Day 7 after surgery

• Tumor regression grade

  Day 7 after surgery

• Objective Response Rate

  Pre-neoadjuvant therapy, Post-neoadjuvant therapy.

• Neoadjuvant rectal score

  Day 7 after surgery

• R0 resection rate

  Day 7 after surgery

Study Arms (2)

mFOLFOX6+Serplulimab

EXPERIMENTAL

Preoperative treatment with mFOLFOX6 chemotherapy combined with Serplulimab (3mg/kg) every 2 weeks, for a total of 6 cycles before surgery.

Drug: mFOLFOX6; Drug: Serplulimab

mFOLFOX6

ACTIVE COMPARATOR

Preoperative treatment with mFOLFOX6 chemotherapy every 2 weeks, for a total of 6 cycles before surgery.

Drug: mFOLFOX6

Interventions

mFOLFOX6 DRUG

Oxaliplatin 85 mg/m², intravenous infusion on Day 1; Fluorouracil 400 mg/m², intravenous infusion on Day 1; Fluorouracil 2400 mg/m², continuous infusion via chemotherapy pump for 46-48 hours; Leucovorin calcium 400 mg/m², intravenous infusion on Day 1 (or Levoleucovorin 200 mg/m², intravenous infusion).

mFOLFOX6; mFOLFOX6+Serplulimab

Serplulimab DRUG

3 mg/kg, intravenous infusion, Day 1.

mFOLFOX6+Serplulimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Rectal cancer patients with MRI showing the lower edge of the tumor within 15 cm of the anal verge, cT3-4 N any or cT any N1/2;
• Pathologically confirmed adenocarcinoma, with pMMR (MLH1, MSH2, MSH6, and PMS2) positivity for all four proteins, or gene testing indicating microsatellite stability;
• No complete bowel obstruction, or proximal colostomy relieving bowel obstruction;
• Aged 18 to 75 years, regardless of gender;
• ECOG performance status: 0-1;
• Expected survival time ≥2 years;
• No previous chemotherapy, radiotherapy, targeted therapy, or immunotherapy;
• Female participants must not be breastfeeding, and pregnancy test results must be negative;
• Voluntary signing of the informed consent form, with the ability to understand and comply with the study requirements.

You may not qualify if:

• Local invasion of surrounding organs by rectal tumor: Imaging tests suggest the tumor directly invades adjacent organs or structures, i.e., tumors with clinical stage cT4 below the peritoneal reflection or cT4b above the peritoneal reflection;
• Patients with distant metastasis;
• Previous treatment with any chemotherapy, radiotherapy, targeted therapy, or immunotherapy;
• Active autoimmune diseases requiring systemic treatment (e.g., corticosteroids or immunosuppressants) within the past 2 years prior to enrollment;
• History of HIV infection, or active chronic hepatitis B or C (high viral DNA load);
• Currently receiving tuberculosis treatment or having received tuberculosis treatment in the past year prior to screening for active tuberculosis;
• Known or suspected allergy to the study drugs or any drug related to the study;
• Severe cardiovascular or cerebrovascular diseases;
• Severe active infection or uncontrollable infection requiring systemic treatment, or unexplained fever \>38.5°C within 14 days before the first dose;
• Systemic corticosteroid treatment or other immunosuppressants within 14 days before the first dose, or immunostimulants within 4 weeks prior to the first dose;
• Clear history of neurological or psychiatric disorders, including epilepsy or dementia;
• Refusal to sign the informed consent form.

Sponsors & Collaborators

• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: lead

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Tingyu Wu, Ph.D.

CONTACT

+86-021-25077855; wutingyu@xinhuamed.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: January 25, 2026
• First Posted: February 2, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP