Cadonilimab plus an anti-angiogenic drug for metastatic dMMR/MSI-H colorectal cancer
An Open and Exploratory Phase Ⅱ Clinical Trial of Cadonilimab Combined With Anti-angiogenic Agents in Metastatic dMMR/MSI-H Colorectal Cancer
We will try cadonilimab together with an anti-angiogenic drug in people with metastatic dMMR/MSI‑H colorectal cancer, including those who are new to PD‑1/PD‑L1 therapy and those who have had it before.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | Fudan University Academic / other |
| Drugs / interventions | envafolimab, lenvatinib, immunotherapy, prednisone, cadonilimab, bevacizumab, fruquintinib |
| Locations | 1 site (Shanghai, China) |
| Trial ID | NCT07003022 on ClinicalTrials.gov |
What this trial studies
This is a prospective, open-label, two-cohort Phase II study enrolling adults with recurrent or metastatic dMMR/MSI‑H colorectal cancer. Participants are assigned to one of two cohorts based on prior PD‑1/PD‑L1 exposure (immune‑naive or immune rechallenge) and receive cadonilimab combined with an anti‑angiogenic agent chosen by the investigator (bevacizumab, regorafenib, or fruquintinib). Treatment continues until unacceptable toxicity, disease progression, withdrawal, death, or other investigator-determined discontinuation. The study measures safety and anti-tumor activity in this population at a single center in Shanghai.
Who should consider this trial
Good fit: Adults 18–80 years with histologically confirmed dMMR/MSI‑H recurrent or metastatic colorectal cancer, ECOG 0–2, at least one measurable lesion, and adequate organ function are eligible, whether they are PD‑1/PD‑L1 naive or previously treated.
Not a fit: Patients with non‑dMMR/MSI‑H tumors, poor organ function, ECOG performance status >2, or contraindications to anti‑angiogenic or immune therapies are unlikely to benefit from this regimen.
Why it matters
Potential benefit: If successful, this combination could shrink tumors and extend the time before the cancer worsens for patients with metastatic dMMR/MSI‑H colorectal cancer, including some who previously failed PD‑1/PD‑L1 therapy.
How similar studies have performed: PD‑1 therapies have shown strong activity in MSI‑H colorectal cancer and combining immune checkpoint blockade with anti‑angiogenic drugs has shown promising signals in other settings, but combinations with cadonilimab are still under active investigation.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: \- Signed written informed consent prior to enrollment. Age 18-80 years. dMMR or MSI-H Diagnosis confirmed by histological examination and/or cytological examination combined with imaging assessment of advanced colorectal cancer. ECOG score: 0 to 2. At least one measurable lesion (≥10 mm long diameter on CT scan for non-lymph node lesions and ≥15 mm short diameter on CT scan for lymph node lesions according to iRECIST criteria). Adequate organ function with. Routine blood: Absolute Neutrophil Count (ANC) 1.5 × 109/L, Platelets (Platelet, PLT) ≥ 100 × 109/L, Hemoglobin (HGB) ≥ 90 g/L. Liver function: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤3×ULN; serum albumin ≥30 g/L; after conventional hepatoprotective treatment meeting the above criteria, and can be stable for at least 1 week after evaluation by the investigator can be enrolled. Renal function: Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/mi (applying the standard Cockcroft-Gault formula). Coagulation function: International Normalized Ratio (INR) ≤ 1.5 /PT ≤ 1.5 × ULN, aPTT ≤ 1.5 × ULN; if the subject is receiving anticoagulation therapy, as long as PT and INR are within the range drawn up by anticoagulant drugs. A predicted survival of ≥ 3 months. Female patients must be non-pregnant and non-lactating and are required to use a medically approved form of contraception (e.g., IUD, pill or condom) during study treatment and for at least 120 days after study completion, and are not allowed to donate eggs to another person or freeze them for fertilization and propagation during this period. Exclusion Criteria: * Symptomatic brain metastases. A prior history of a primary tumor outside of the colorectal cancer in 3 years Active autoimmune disease or autoimmune disease with potential for recurrence such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, previous thyroid surgery cannot be included; subjects with vitiligo or complete remission of asthma in childhood and adult who do not require any intervention afterwards can be included; subjects with asthma requiring medical intervention with bronchodilators cannot be included. Subjects with any severe and/or uncontrolled disease. including. Poorly controlled blood pressure (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg); poorly controlled diabetes (fasting blood glucose \[FBG\] \> 10 mmol/L) Having ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥ 470ms) and ≥ grade 2 congestive heart failure (New York Heart Association \[NYHA\] classification) Active or uncontrolled severe infection (≥ CTCAE grade 2 infection) requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection Active hepatitis (transaminases do not meet the inclusion criteria, hepatitis B reference: HBV DNA ≥ 1000 IU/ml or ≥ 10\^4 copies/ml; hepatitis C reference: HCV RNA ≥ 1000 IU/ml or ≥ 10\^4 copies/ml; after nucleotide based antiviral therapy below the above criteria, can be enrolled); chronic hepatitis B virus carriers with HBV DNA \< 10\^4 IU/ml, who must receive concomitant antiviral therapy during the trial to be enrolled. Those with renal failure requiring hemodialysis or peritoneal dialysis. Those with a history of immunodeficiency, including HIV-positive or suffering from other acquired or congenital immunodeficiency diseases, or a history of organ transplantation Active autoimmune disease requiring systemic therapy (e.g., use of disease-relieving drugs, corticosteroids, or immunosuppressive agents) within 2 years prior to the start of study treatment, except for replacement therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency); receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy. Doses \>10 mg/day of prednisone or other equivalent hormone and within 2 weeks of the first dose and still continuing Those with a history of active tuberculosis Those who fail to control and still require repeated drainage of ascites, pericardial effusion, pleural effusion. Research treatment related to. Patients who have undergone major organ transplantation Those who have undergone major surgical treatment, incisional biopsy or significant traumatic injury within 28 days prior to the start of study treatment; or have a long-standing untreated wound or fracture History of live attenuated vaccination within 14 days prior to the start of study treatment or planned live attenuated vaccination during the study History of severe hypersensitivity reactions following the use of monoclonal antibodies; known hypersensitivity to active ingredients or excipients such as envafolimab, lenvatinib, etc., of this study drug Those who are participating or have participated in other clinical studies within 4 weeks prior to the start of the study Those who have received PD-1/CTLA-4 dual immunotherapy during previous treatment. Those with a history of severe allergy. Women who are pregnant or breastfeeding At risk for bleeding, or with coagulation disorders, or undergoing thrombolytic therapy Those with a history of psychotropic substance abuse and unable to abstain or with psychiatric disorders Subjects who, in the judgment of the investigator, have a concomitant disease that seriously jeopardizes the safety of the subject or interferes with the completion of the study, or subjects for whom other reasons are deemed to exist that make them unsuitable for enrollment In the judgment of the investigator, subjects who, in the judgment of the investigator, have a concomitant disease that seriously jeopardizes the safety of the subject or interferes with the completion of the study, or subjects for whom other reasons are deemed to exist that make them unsuitable for enrollment.
Where this trial is running
Shanghai, China
- Fudan University Shanghai Cancer Center — Shanghai, China, China (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.