A Dose-Expansion Trial of Intravenous HNF4α srRNA for Unresectable or Metastatic Colorectal Cancer

NCT07050394 | Recruiting Early Phase 1

• 1 other identifier: CZXH-CRC-2025-IIT
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm, open-label, exploratory clinical trial. Building on the previous dose-escalation trial, this dose-expansion trial aims to evaluate the safety and tolerability of intravenous monotherapy with CD-GA-102 or its combination with immunotherapy and other systemic treatments in patients with unresectable locally advanced or metastatic colorectal cancer, and to preliminarily explore its efficacy in treating colorectal cancer.

Conditions

Colorectal Cancer Metastatic; Colorectal Cancer Recurrent; Colorectal Cancer Stage IV

Keywords

Colorectal Cancer; Hepatocyte nuclear factor 4α; Differentiation therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate，ORR

  Evaluate the objective response rate of HNF4α srRNA monotherapy or in combination with immunotherapy and other systemic treatments in patients with metastatic colorectal cancer, according to the RECIST v1.1 criteria

  From the first study dose date until the date of documented complete response or partial response, assessed up to 24 months

Secondary Outcomes (12)

• Safty and tolerability

  Through study completion, an average of 2 years

• Duration of Response (DOR)

  up to 24 months

• Progression-Free Survival，PFS

  up to 24 months

• Time To Progression，TTP

  up to 24 months

• Time To Response，TTR

  up to 24 months

Study Arms (1)

CD-GA-102

EXPERIMENTAL

A lipid nanoparticle-encapsulated self-replicating RNA encoding hepatocyte nuclear factor 4α

Drug: CD-GA-102

Interventions

CD-GA-102 DRUG

CD-GA-102 will be administered intravenously at 50 μg per dose, with dosing scheduled at 2 weeks (±3 days) and 4 weeks (±3 days) after the initial dose, followed by maintenance therapy every 3 weeks (±3 days). Dosing intervals may be adjusted based on participant tolerability and safety. After receiving at least two doses of CD-GA-102 monotherapy and completing safety assessments, participants may be offered combination therapies, as determined by the investigator.

CD-GA-102

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, regardless of gender.
• Patients with colorectal cancer confirmed by histology or cytology.
• Patients with unresectable locally advanced or metastatic colorectal cancer.
• Patients who are not suitable for or intolerant of standard systemic therapy; or patients who have progressed after receiving standard systemic therapy (including but not limited to the following regimens) as confirmed by RECIST v1.1: chemotherapy based on fluorouracil, oxaliplatin, or irinotecan, and targeted drugs such as anti-VEGF/EGFR monoclonal antibodies.
• According to RECIST v1.1, patients must have at least one measurable lesion. Lesions that have received local treatment (including surgery, radiotherapy, TACE, and ablation) cannot be selected as target lesions, unless the lesion is the only measurable lesion and has clearly progressed according to imaging, in which case it may be considered as a target lesion.
• Life expectancy ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.
• Fertile male participants and women of childbearing age must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose of the investigational drug. Women of childbearing age include premenopausal women and women within 2 years of menopause. Women of childbearing age must have a negative serum pregnancy test within ≤7 days before the first dose of the investigational drug.
• Willing to sign the written informed consent form and voluntarily comply with the protocol.

You may not qualify if:

• Patients who have completed standard adjuvant chemotherapy after tumor resection and relapsed or developed metastasis after a drug-free interval of 6 months, and have not received standard systemic therapy.
• Patients with tumor tissue testing confirming mismatch repair deficiency or high microsatellite instability (dMMR/MSI-H) who have not received immune checkpoint inhibitor treatment (PD-1 monoclonal antibody or PD-L1 monoclonal antibody).
• Patients with clinical or radiological evidence of current intestinal obstruction, perforation, or bleeding; or patients assessed by the investigator to be at high risk of perforation or bleeding.
• Serum albumin \< 28 g/L, or bilirubin \> 3×ULN, or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) \> 5×ULN.
• Patients with significant renal impairment, serum creatinine \> 1.5×ULN, or creatinine clearance \< 40 mL/min; urine protein \<2+ (if urine protein ≥2+, a 24-hour urine protein quantification is required, and patients with 24-hour urine protein quantification \<1 g may be eligible).
• Absolute neutrophil count \< 1.5×10\^9/L, or platelets \< 50×10\^9/L, or hemoglobin \< 9 g/dL.
• International Normalized Ratio (INR) \> 2.
• Patients with known brain metastases from tumors.
• Patients with uncontrolled hypertension, diabetes, or other severe cardiac or pulmonary diseases, or severe organ dysfunction.
• Patients who have received local or systemic anti-tumor treatments (including immunotherapy, targeted therapy, or chemotherapy) within 4 weeks, or radiotherapy within 3 weeks, except for treatment regimens assessed as disease progression according to RECIST (version 1.1) criteria.
• Patients with adverse events related to previous local or systemic anti-tumor treatments still ≥ Grade 2 (excluding alopecia and other events deemed tolerable by the investigator).
• Patients with uncontrollable active infections (e.g., pulmonary or abdominal infections).
• Patients with malignancies other than colorectal cancer within the past 5 years, with the exception of low-risk malignancies with a low risk of metastasis or death (estimated 5-year overall survival \> 90%), such as early gastrointestinal cancer treated effectively, cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, etc.
• Patients with active autoimmune diseases requiring systemic therapy within the past 2 years, or autoimmune diseases judged by the investigator to have a potential for recurrence or planned treatment, including but not limited to inflammatory bowel disease, celiac disease, Wegener's granulomatosis, Hashimoto's thyroiditis, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis.
• Patients who require systemic treatment with corticosteroids (prednisone or equivalent \> 10 mg/day) or other immunosuppressive drugs within 14 days before the first dose of the investigational drug.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Study Sites (1)

Shanghai Changzheng Hospital

Shanghai, None Selected, 200003, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• Weifen Xie, MD. PhD

  Naval Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wen-Ping Xu, MD. PhD

CONTACT

+862115026590980; xwp198527@sina.com

Weifen Xie, MD. PhD

CONTACT

+862113701682806; weifenxie@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: July 3, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)