A Clinical Study to Evaluate the Efficacy and Safety of Envafolimab Combined With Cetuxima-βand mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)

NCT06959693 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SMA CRC 005
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective randomized controlled Phase Ⅱ/Ⅲ Clinical study to evaluate the clinical efficacy and safety of Envafolimab combining with Cetuximab -β and mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)

Conditions

Metastatic Colorectal Cancer (CRC)

Outcome Measures

Primary Outcomes (1)

• Progressin Free Survival，PFS

  Progression-free survival based on RECIST v1.1

  Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 3 years

Secondary Outcomes (5)

• OS，Overall survival

  from the date of first dose unitl the date of death from any cause，assessed up to 3 years

• ORR， Objective response

  up to 3 years

• DCR， Disease control rate

  up to 1 year

• NED Rate， No Evidence of Disease Rate

  up to 3 years

• Safety(Adverse Event (AE) Incidence)

  up to 3 years

Study Arms (2)

Envafolimab combining with Cetuximab -β and mFOLFOX6

EXPERIMENTAL

Drug: Cetuxima-β; Drug: Envafolimab; Drug: mFOLFOX6

Cetuximab -β and mFOLFOX6

ACTIVE COMPARATOR

Drug: Cetuxima-β; Drug: mFOLFOX6

Interventions

Cetuxima-β DRUG

500 mg/m², initial intravenous infusion (IV)\>120 min, subsequent IV \>60 min , D1，every 2 weeks

Cetuximab -β and mFOLFOX6; Envafolimab combining with Cetuximab -β and mFOLFOX6

Envafolimab DRUG

a single fixed dose of 200 mg, subcutaneous injection(SC), every 2 weeks (Day 1 of each cycle \[D1\])

Envafolimab combining with Cetuximab -β and mFOLFOX6

mFOLFOX6 DRUG

Oxaliplatin 85 mg/m² , IV, over 120 min, Day 1; Leucovorin 400 mg/m² (or Calcium Folinate 200 mg/m²), IV, over 120 min, D1; 5-FU 400 mg/m² , bolus injection, followed by 1200 mg/(m²·d) continuous IV for 2 days (total dose 2400 mg/m² over 46 - 48 hours)

Cetuximab -β and mFOLFOX6; Envafolimab combining with Cetuximab -β and mFOLFOX6

Eligibility Criteria

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

You may qualify if:

• Patients are eligible for the study if they meet all of the following criteria:
• Prior to enrollment, the participant is required to sign a written informed consent form.
• Participants should be above 18 years，regardless of gender.
• Histopathologically confirmed untreated advanced colorectal adenocarcinoma.
• Tumors with RAS (KRAS, NRAS, HRAS) and BRAF wild-type, MSS phenotype, excluding appendiceal or anal cancer. All listed codons must be wild-type: KRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146) ; NRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146)
• Imaging (enhanced CT/MRI/PET-CT) confirms advanced/metastatic colorectal cancer with measurable lesions according to RECIST v1.1.
• No prior systemic therapy for advanced/metastatic colorectal cancer, including chemotherapy, EGFR inhibitors (cetuximab, panitumumab), VEGF inhibitors (bevacizumab), and immune checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4). Adjuvant/neoadjuvant chemotherapy within 6 months before recurrence/metastasis is considered first-line therapy.
• ECOG PS score 0-1.
• Expected survival \>12 weeks.
• Adequate organ function (without blood component or growth factor use within 14 days):
• Hematology:Neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L. Liver/kidney function: SCr ≤1.5×ULN or creatinine clearance ≥50 ml/min, TBIL ≤1.5×ULN, AST/ALT ≤2.5×ULN (≤5×ULN if due to liver metastasis), urine protein \<2+ (≤1g/24h if ≥2+).
• Normal coagulation, no active bleeding/thrombosis: INR ≤1.5×ULN, APTT ≤1.5×ULN, PT ≤1.5×ULN.
• Non-surgically sterile women of childbearing potential must use contraception during and 3 months after treatment; serum/urine HCG negative within 7 days before enrollment; not breastfeeding. Non-surgically sterile men must use contraception with partners during and 3 months after treatment.
• Willing participant with good compliance for safety and survival follow-up.

You may not qualify if:

• Other malignancies in the past or current (excluding cured basal cell carcinoma or cervical carcinoma in situ).
• Current duodenal ulcer, ulcerative colitis, intestinal obstruction, or other GI conditions that may cause bleeding or perforation, as judged by the investigator.
• Patients with symptomatic pleural, peritoneal, or pericardial effusions requiring treatment.
• History of allergy to monoclonal proteins or any component of the study drugs.
• Oral traditional Chinese medicine, immunomodulators within 2 weeks, or radiotherapy within 4 weeks before treatment.
• Thyroid dysfunction that is uncontrolled by medication.
• Uncontrolled hypertension despite receiving optimal treatment (systolic BP\>150 mmHg or diastolic BP\>90 mmHg).
• Uncontrolled cardiac conditions: (1) NYHA Class II+ heart failure; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant arrhythmias requiring treatment.
• Active autoimmune disease or a history of such diseases.
• Immunosuppressants, systemic, or absorbable topical steroids for immunosuppression (\>10 mg/day prednisone or equivalent) within 2 weeks before enrollment.
• CNS metastases.
• Active infection or unexplained fever\>38.5°C during screening or before first dose (tumor-related fever is acceptable).
• History or current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, or severe pulmonary dysfunction.
• Live vaccine administration within 4 weeks before first dose or planned during the study.
• History of psychiatric drug abuse, alcoholism, or drug addiction.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Medical Oncology,Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510075, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

envafolimab

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

Central Study Contacts

Ruihua Xu, PhD

CONTACT

+86-13922206676; xurh@sysucc.org.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: President and Professor

Model Details: Experimental Arm: Cetuximab β + mFOLFOX6 + Envafolimab • Induction Phase (12 cycles): o Patients receive cetuximab β + mFOLFOX6 + envafolimab. o Patients who achieve CR/PR/SD (no disease progression) after 12 cycles proceed to the maintenance phase. • Maintenance Phase: o Cetuximab β + 5-FU + envafolimab Control Arm: Cetuximab β + mFOLFOX6 • Induction Phase (12 cycles): o Patients receive cetuximab β + mFOLFOX6. o Patients who achieve CR/PR/SD (no disease progression) after 12 cycles proceed to the maintenance phase. • Maintenance Phase: o Cetuximab β + 5-FU

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 6, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): June 30, 2030
• Last Updated: May 6, 2025

Record last verified: 2025-04

Locations

CN (1)