Actively Recruiting
Neoadjuvant Treatment of Fulzerasib Plus Cetuximab N01 in KRAS G12C Mutated Locally Advanced Colorectal Cancer With or Without Resectable Metastases
Led by Zhejiang University · Updated on 2026-05-12
40
Participants Needed
1
Research Sites
291 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Background：KRAS mutations are the most common genetic alterations in colorectal cancer (CRC), associated with aggressive tumor biology and poor prognosis. For metastatic CRC harboring KRAS mutations, first-line standard treatment is chemotherapy plus bevacizumab. However, its anti-angiogenic effects contraindicate perioperative use. KRAS G12C, the first druggable KRAS target, accounts for \~3% of CRC KRAS mutations. KRAS G12C inhibitor monotherapy shows efficacy in post-standard-therapy metastatic CRC, while combination with RAS-MAPK pathway blockade demonstrates superior efficacy. Based on promising frontline data combining KRAS G12C inhibitors with anti-EGFR antibodies in metastatic CRC, we evaluate neoadjuvant fulzerasib plus cetuximab N01 in locally advanced KRAS G12C-mutated CRC, with or without resectable metastases. Methods：Single-arm, multicenter, phase II trial (N=40). Eligibility: age 18-80 years, ECOG 0-1, histologically confirmed colorectal adenocarcinoma (stages T4N0-2M0, T3N2M0, T0-4N0-2M1a \[resectable metastases confirmed by multidisciplinary discussion\]), KRAS G12C mutation, NRAS/BRAF wild-type, pMMR/MSS. Neoadjuvant therapy: fulzerasib (qd, po, d1-28) plus cetuximab N01 (500 mg/m², IV, q2w) for 2 months. Safety assessments (CBC, liver/renal function, QoL) every 2 weeks; CEA monthly. Tumor response assessed by CT chest/abdomen and rectal MRI at 2 months. Radical surgery for responders (cCR patients may choose watchful waiting). Adjuvant therapy per pathological response. Follow-up: CEA every 3 months, CT every 6 months. Primary endpoint: overall response rate (pCR or cCR). Secondary endpoints: ORR, 1-year DFS, 3-year DFS, QoL. RECIST v1.1 for disease assessment; NCI-CTCAE v5.0 for adverse events. Hypothesis：This chemotherapy-free neoadjuvant regimen combining a KRAS G12C inhibitor with cetuximab N01 may enhance perioperative safety and improve prognosis and quality of life in patients with KRAS G12C-mutated CRC.
CONDITIONS
Official Title
Neoadjuvant Treatment of Fulzerasib Plus Cetuximab N01 in KRAS G12C Mutated Locally Advanced Colorectal Cancer With or Without Resectable Metastases
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 80 years with ECOG performance status 0-1
- Histologically confirmed colorectal adenocarcinoma with staging T4N0-2M0, T3N2M0, or T0-4N0-2M1a with resectable metastases
- Presence of KRAS G12C mutation, NRAS and BRAF wild-type, and proficient mismatch repair/microsatellite stability
- No prior systemic treatment for locally advanced colorectal cancer; no prior targeted therapy if metastatic lesions are resectable
- Adequate blood counts: hemoglobin 60; 90g/L, neutrophils 60; 1.5x10^9/L, platelets 60; 75x10^9/L
- Liver and kidney function within specified limits (bilirubin 64; 1.5x ULN, ALT/AST 64; 2.5x ULN, creatinine 64; 1.5x ULN or clearance 60; 50ml/min)
- Coagulation and thyroid function within normal limits
- Cardiac function with left ventricular ejection fraction 60; 50%
You will not qualify if you...
- Presence of MSI-H or deficient mismatch repair
- Multiple unresectable metastases
- Other active malignancies within past 3 years except certain cured non-invasive cancers
- Active inflammatory bowel disease within 4 weeks before enrollment
- Uncontrolled pleural, pericardial effusions, or ascites requiring repeated drainage
- Toxic reactions above grade 1 from previous anti-tumor treatment (except certain neurotoxicity or hair loss)
- Recent bleeding events 63; grade 3 within 4 weeks
- Arterial or venous thrombotic events within past 6 months
- History of substance abuse with inability to quit
- Severe uncontrolled diseases including uncontrolled hypertension, significant heart disease, severe infections, cirrhosis, active hepatitis requiring treatment, renal failure needing dialysis, immunodeficiency, poorly controlled diabetes, significant proteinuria, or treated neurological/psychiatric disorders
- Prior targeted therapies including G12C inhibitors or bevacizumab
- Any other conditions judged by investigators to pose significant risk or interfere with study completion
AI-Screening
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Trial Site Locations
Total: 1 location
1
Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China, 310000
Actively Recruiting
Research Team
K
Kefeng Ding, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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