Intravenous HNF4α srRNA (CD-GA-102) for unresectable or metastatic colorectal cancer

A Dose-expansion Trial Exploring the Safety and Efficacy of Intravenous HNF4α srRNA in Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer

This trial will try IV CD-GA-102 (HNF4α srRNA) alone or with other cancer medicines to see if it is safe and can help adults with unresectable or metastatic colorectal cancer who have progressed on or cannot tolerate standard treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Shanghai, None Selected)
• Trial ID: NCT07050394 on ClinicalTrials.gov

What this trial studies

This single-arm, open-label dose-expansion trial administers CD-GA-102 by peripheral IV at 50 μg per dose with an initial schedule of doses at baseline, about 2 weeks, and about 4 weeks, then maintenance every three weeks with possible interval adjustments for tolerability. After at least two monotherapy doses and completion of a safety assessment, investigators may add immune checkpoint inhibitors, targeted therapy, or other systemic treatments based on clinical judgment. Up to approximately 20 participants with measurable unresectable or metastatic colorectal cancer will be enrolled and followed for safety and antitumor activity using RECIST v1.1. The trial builds on a prior dose‑escalation phase to further characterize tolerability and explore preliminary efficacy.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable locally advanced or metastatic colorectal cancer, at least one measurable lesion by RECIST v1.1, life expectancy ≥12 weeks, and who are intolerant of or have progressed after standard systemic therapy are the intended participants.

Not a fit: Patients who are eligible for effective standard-of-care or curative treatments, have resectable disease, or have poor performance status or significant organ dysfunction are unlikely to benefit from this early-phase experimental therapy.

Why it matters

Potential benefit: If successful, CD-GA-102 could provide a new differentiation-targeted treatment option for patients with advanced colorectal cancer who have limited standard therapy choices.

How similar studies have performed: This therapeutic approach is relatively novel in colorectal cancer; a prior dose‑escalation phase has yielded initial safety data but definitive efficacy for HNF4α srRNA remains unproven.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years, regardless of gender.
2. Patients with colorectal cancer confirmed by histology or cytology.
3. Patients with unresectable locally advanced or metastatic colorectal cancer.
4. 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.
5. 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.
6. Life expectancy ≥ 12 weeks.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.
8. 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.
9. Willing to sign the written informed consent form and voluntarily comply with the protocol.

Exclusion Criteria:

1. 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.
2. 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).
3. 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.
4. Serum albumin \< 28 g/L, or bilirubin \> 3×ULN, or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) \> 5×ULN.
5. 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).
6. Absolute neutrophil count \< 1.5×10\^9/L, or platelets \< 50×10\^9/L, or hemoglobin \< 9 g/dL.
7. International Normalized Ratio (INR) \> 2.
8. Patients with known brain metastases from tumors.
9. Patients with uncontrolled hypertension, diabetes, or other severe cardiac or pulmonary diseases, or severe organ dysfunction.
10. 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.
11. 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).
12. Patients with uncontrollable active infections (e.g., pulmonary or abdominal infections).
13. 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.
14. 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.
15. 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.
16. Patients who are preparing for or have previously undergone allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
17. Patients who are positive for HBV-DNA or HCV RNA.
18. Patients with known active tuberculosis. Patients suspected of having active tuberculosis must be excluded based on chest imaging, sputum tests, and clinical symptoms and signs.
19. Patients who are positive for human immunodeficiency virus (HIV).
20. Pregnant or breastfeeding women, or women who cannot rule out the possibility of pregnancy.
21. Patients who have participated in other drug trials within the past 4 weeks.
22. Other situations deemed by the investigator as unsuitable for participation in this clinical trial.

Where this trial is running

Shanghai, None Selected

• Shanghai Changzheng Hospital — Shanghai, None Selected, China (Recruiting)

Study contacts

• Principal investigator: Weifen Xie, MD. PhD — Naval Medical University
• Study coordinator: Wen-Ping Xu, MD. PhD

Conditions Colorectal Cancer Metastatic; Colorectal Cancer Recurrent; Colorectal Cancer Stage IV; Colorectal Cancer; Hepatocyte nuclear factor 4α; Differentiation therapy