Savolitinib Plus Cetuximab and FOLFOX Chemotherapy for RAS/BRAF Wild-type Metastatic Colorectal Cancer

NCT07683403 | Not Yet Recruiting Phase 1

• 1 other identifier: HMPL-504-SUMMER-C101
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of this clinical trial is to learn if adding savolitinib to cetuximab plus FOLFOX chemotherapy works as a first-line treatment for patients with RAS/BRAF wild-type metastatic colorectal cancer, and to evaluate its safety. The main questions it aims to answer are: Does the addition of savolitinib improve the objective response rate (ORR) compared to cetuximab plus FOLFOX alone? What medical problems (adverse events) do participants experience when taking savolitinib in combination with cetuximab and FOLFOX? Researchers will compare savolitinib plus cetuximab and FOLFOX (experimental group) versus cetuximab and FOLFOX alone (control group) to see if the triplet regimen provides better tumor response and survival outcomes. Participants will: Take oral savolitinib once daily in repeated 14-day cycles (or receive control treatment), combined with weekly cetuximab and bi-weekly FOLFOX chemotherapy Visit the clinic every 2 weeks or 4 weeks for treatment administration, safety monitoring, and laboratory tests Undergo tumor imaging assessments every 8 weeks (4 cycles) to evaluate treatment response and disease progression Have regular follow-up visits for 30 days after the last dose, and then every 3 months for survival follow-up

Conditions

Colorectal Cancer (CRC)

Keywords

savolitinib; Colorectal cancer; cetuximab; c-MET

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The incidence of confirmed complete response or partial response

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 24 months)

Secondary Outcomes (6)

• Progression free survival (PFS)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 24 months)

• Disease control rate (DCR)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 24 months)

• Duration of response (DOR)

  From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 24 months)

• Time to response (TTR)

  From date of first dose of study drug until partial response (up to approximately 12 months)

• Overall survival (OS)

  From date of first dose of study drug until withdrawal of consent or death (up to approximately 24 months)

Study Arms (2)

Savolitinib plus cetuximab and FOLFOX chemotherapy

EXPERIMENTAL

Drug: Savolitinib plus cetuximab and FOLFOX chemotherapy

Cetuximab plus FOLFOX chemotherapy

ACTIVE COMPARATOR

Drug: Cetuximab and FOLFOX chemotherapy

Interventions

Savolitinib plus cetuximab and FOLFOX chemotherapy DRUG

Savolitinib dosing regimen: 200mg, qd, po. Cetuximab: Administered intravenously at an initial dose of 400 mg/m² prior to chemotherapy, followed by a weekly dose of 250 mg/m² infused over 1 hour. FOLFOX chemotherapy regimen: Oxaliplatin 85 mg/m² intravenously over 2 hours on Day 1; leucovorin (LV) 400 mg/m² intravenously over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus on Day 1, followed by continuous intravenous infusion of 1200 mg/(m²·day) for 2 days (total dose 2400 mg/m², infused over 46-48 hours).

Savolitinib plus cetuximab and FOLFOX chemotherapy

Cetuximab and FOLFOX chemotherapy DRUG

Cetuximab: Administered intravenously at an initial dose of 400 mg/m² prior to chemotherapy, followed by a weekly dose of 250 mg/m² infused over 1 hour. FOLFOX chemotherapy regimen: Oxaliplatin 85 mg/m² intravenously over 2 hours on Day 1; leucovorin (LV) 400 mg/m² intravenously over 2 hours on Day 1; 5-FU 400 mg/m² intravenous bolus on Day 1, followed by continuous intravenous infusion of 1200 mg/(m²·day) for 2 days (total dose 2400 mg/m², infused over 46-48 hours).

Cetuximab plus FOLFOX chemotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntarily sign the informed consent form after fully understanding this study;
• Aged 18 to 75 years (inclusive), male or female;
• Have at least one measurable lesion (RECIST 1.1);
• Histologically confirmed unresectable locally advanced or metastatic colorectal cancer;
• pMMR by immunohistochemistry or unknown MMR protein expression status;
• KRAS/NRAS and BRAF all wild-type;
• c-MET IHC intensity score 2+ or 3+ in ≥50% of tumor cells in the primary lesion; or positive by FISH; or NGS copy number ≥3;
• No prior systemic therapy (Note: prior neoadjuvant or adjuvant chemotherapy is allowed if disease progression/recurrence occurred during or ≥6 months after completion of such therapy);
• ECOG performance status 0-1;
• Life expectancy ≥12 weeks;
• Laboratory parameters (within 14 days without blood transfusion):
• Absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥9 g/dL;
• Liver function: AST and ALT ≤2.5×ULN, total bilirubin ≤1.5×ULN; if liver metastases present, AST and ALT ≤5×ULN;
• Renal function: serum creatinine ≤1.5×ULN, creatinine clearance (CCr) ≥60 mL/min;
• Fertile male or female patients voluntarily agree to use effective contraceptive methods during the study and for 6 months after the last dose of study treatment.

You may not qualify if:

• Prior treatment with anti-EGFR monoclonal antibody therapy;
• Prior treatment with c-MET small molecule inhibitors or monoclonal antibodies targeting c-MET or HGF;
• Received approved or investigational systemic anti-tumor therapy within 4 weeks prior to enrollment;
• Participated in another clinical trial of a drug not yet approved or marketed in China and received the investigational drug within 4 weeks prior to enrollment;
• Underwent any surgery or invasive treatment or procedure (except venous catheterization, puncture drainage, etc.) within 4 weeks prior to enrollment;
• INR \>1.5 or APTT \>1.5×ULN;
• Clinically significant electrolyte abnormalities as judged by the investigator;
• Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg);
• Poorly controlled blood glucose (FBG ≥10 mmol/L);
• Any disease or condition affecting drug absorption, or inability to take oral savolitinib;
• Active gastric or duodenal ulcer, ulcerative colitis, or other gastrointestinal diseases, or active bleeding from an unresected tumor, or other conditions that may cause gastrointestinal bleeding or perforation within 28 days prior to enrollment;
• History or evidence of significant bleeding tendency within 3 months prior to enrollment (bleeding \>30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (\>5 mL fresh blood within 4 weeks), or thromboembolic events within 12 months;
• Clinically significant cardiovascular disease (e.g., acute myocardial infarction within 6 months, unstable angina, heart failure NYHA class \>2, ventricular arrhythmia requiring medication, LVEF \<50%);
• Other malignancy within the past 5 years (except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix);
• Active or uncontrolled serious infection:

Sponsors & Collaborators

• Fudan University: lead

Study Sites (5)

Changhai Hospital

Shanghai, 200000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200000, China

Location

Renji Hospital, Shanghai Jiao Tong University, School of Medicine

Shanghai, 200000, China

Location

Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine

Shanghai, 200000, China

Location

Zhongshan Hospital, Fudan University

Shanghai, 200000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; Cetuximab

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

Central Study Contacts

Jianmin Xu, Phd

CONTACT

021-64041990; xujmin@yahoo.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: prospective, randomized, controlled, multicenter, open-label study

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: July 6, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)