Combination treatment for advanced colorectal cancer

Cadonilimab in Combination With Bevacizumab and FOLFOX Regimen for the First-Line Treatment of Advanced Unresectable MSS-Type, RAS-Mutated Metastatic Colorectal Cancer: A Single-Arm, Open-Label, Multicenter Phase II Study

This study is testing a new combination treatment for people with advanced colorectal cancer to see if it helps them live longer without their cancer getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, bevacizumab, Cadonilimab
• Locations: 1 site (Shanghai)
• Trial ID: NCT06218810 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of a combination therapy using Cadonilimab, Bevacizumab, and the FOLFOX regimen for patients with advanced unresectable MSS-type, RAS-mutated metastatic colorectal cancer. The study aims to evaluate the one-year progression-free survival rate, overall response rate, perioperative safety, and long-term survival outcomes. It involves a multicenter, prospective, single-arm design, focusing on patients who have not previously received systemic anti-tumor therapy. The trial also includes an analysis of patient transcriptomics and immune microenvironment characteristics to inform future treatment strategies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with RAS-mutated, unresectable metastatic colorectal cancer who have not received prior systemic therapy.

Not a fit: Patients with brain metastases or those who have previously undergone systemic anti-tumor therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients with advanced colorectal cancer.

How similar studies have performed: Previous studies have shown promising results with similar immunotherapy combinations, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign a written ICF.
2. Age at enrollment: ≥ 18 years old, ≤ 75 years old, both male and female.
3. The Eastern Cancer Collaborative Organization (ECOG) has a physical fitness score of 0 or 1.
4. The expected survival period is ≥ 3 months.
5. Subjects diagnosed with metastatic colorectal adenocarcinoma by histology or cytology.
6. Colorectal cancer patients who have not received systematic anti-tumor therapy in the past and are not suitable for radical surgical resection or local treatment.
7. Genetic testing results indicate pMMR or MSS; RAS mutation;
8. According to RECIST v1.1, there is at least one measurable lesion that is suitable for repeated and accurate measurements. Note: Brain metastases cannot be used as target lesions; For lesions that have received radiation therapy before, it is not recommended to select them as target lesions. If there are no other lesions that meet the target lesion criteria, and the lesion can be measured according to RECIST v1.1 and there is objective evidence to prove significant progression after radiation therapy, the irradiated lesion can be considered as a target lesion.

Exclusion Criteria:

1. Patients with known MSI-H or dMMR.
2. Participants of RAS wild-type.
3. Subjects suffered from other malignant tumors within 3 years before enrollment, except for cured local tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, etc.).
4. Simultaneously enroll in another clinical study, unless it is an observational, non-interference clinical study or a follow-up period of an intervention study.
5. Received systematic anti-tumor therapy (chemotherapy) within 3 weeks prior to the first administration; Palliative local treatment was performed on non target lesions within 2 weeks prior to the first administration; Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks before the first administration; Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications was received within 1 week before the first administration.
6. Have received any immunotherapy against tumors in the past, including immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any treatment targeting the immune mechanism of tumors.
7. Patients with active autoimmune diseases that require systematic treatment within the past two years (such as using medication to improve the condition, corticosteroids, immunosuppressive agents), and replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) are not considered as systematic treatment.
8. A history of active or previous inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).
9. History of immunodeficiency; HIV antibody test positive individuals; Currently using systemic corticosteroids or other immunosuppressants for a long time.
10. Subjects who are known to have active pulmonary tuberculosis (TB) and suspected to have active TB need to undergo clinical examination to exclude them; Known active syphilis infection.
11. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
12. Previous or current non infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid treatment.

Where this trial is running

Shanghai

• Zhongshan hosptial, Fudan University — Shanghai, China (Recruiting)

Conditions Metastatic Colorectal Cancer; Microsatellite Stable Colorectal Carcinoma; RAS Mutation; Cadonilimab