CEA-targeted CAR-T therapy for advanced CEA-positive solid tumors

A Clinical Study to Evaluate the Safety and Efficacy of CEA-Targeted Chimeric Antigen Receptor T (CAR-T) Cells in Patients With CEA-Positive Advanced Malignant Solid Tumors

This trial will try a CEA-targeted CAR-T cell therapy in adults with advanced, CEA-positive non-small cell lung cancer or breast cancer who have progressed after standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07250386 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label phase 1 trial with two parallel administration groups: intravenous infusion and intrapleural infusion for patients with pleural disease. Each group has a dose-escalation phase using 3–6 patients per dose level followed by a dose-expansion phase at the recommended dose to further evaluate safety and preliminary activity. The study will collect safety, pharmacokinetics, and early efficacy signals (tumor response by RECIST) in patients with tumor CEA positivity. Eligible patients must have CEA positivity by IHC or elevated serum CEA and measurable disease or malignant pleural effusion for the chest infusion subgroup.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically or cytologically confirmed advanced, metastatic, or recurrent non-small cell lung cancer or breast cancer that is CEA-positive and has progressed after at least two lines of standard therapy are the intended candidates.

Not a fit: Patients whose tumors are CEA-negative, those with early-stage disease, or those with medical conditions that preclude CAR-T infusion or the required monitoring are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could offer a new targeted immunotherapy option to shrink or control CEA-positive advanced tumors after other treatments have failed.

How similar studies have performed: CEA-targeted CAR-T approaches and CAR-T therapies in solid tumors have shown limited, early-phase signals but remain experimental with mixed results and ongoing safety challenges.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 years or older, of any gender.
2. Histologically or cytologically confirmed advanced, metastatic, or recurrent solid tumors, including non-small cell lung cancer and breast cancer.
3. Disease progression or intolerance after at least second-line standard therapy, including but not limited to surgery, chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
4. CEA positivity confirmed by immunohistochemistry (IHC) in tumor samples within 3 months of screening (clear membrane staining, with positivity rate ≥10%). If the IHC result is more than 3 months old, serum CEA must be above 10 ng/mL.
5. At least one evaluable lesion according to RECIST 1.1, with a longest diameter of ≥10 mm for non-lymph node lesions and a shortest diameter of ≥15 mm for lymph node lesions. Malignant pleural effusion is acceptable for the chest infusion subgroup.
6. For patients with malignant pleural effusion, accurate volume assessment of pleural effusion by imaging (CT or MRI) and cytological or thoracoscopic biopsy confirmation of malignant pleural effusion.
7. ECOG performance status of 0-2.
8. Life expectancy of 12 weeks or more.
9. No serious psychiatric disorders.
10. The following organ function criteria should be met unless otherwise specified:

    1. Hematology: White blood cell count \>2.0×10\^9/L, neutrophils \>1.0×10\^9/L, lymphocytes \>0.5×10\^9/L, platelets \>50×10\^9/L, hemoglobin \>80 g/L.
    2. Cardiac function: Echocardiography showing ejection fraction ≥50%, with no significant abnormalities on ECG.
    3. Renal function: Serum creatinine ≤2.0×ULN.
    4. Liver function: ALT and AST ≤3.0×ULN (≤5.0×ULN for those with liver tumor infiltration).
    5. Total bilirubin ≤2.0×ULN.
    6. Oxygen saturation \>92% without supplemental oxygen.
11. Eligible for single or venous blood collection with no contraindications to cell collection.
12. Consent to use a reliable and effective method of contraception for 1 year after CAR-T cell infusion (excluding the rhythm method).
13. The participant or their authorized guardian agrees to participate in the clinical trial and signs the informed consent form (ICF), indicating an understanding of the trial's purpose and procedures.

Exclusion Criteria:

1. Clinical symptoms of CNS metastasis or meningeal metastasis at screening, or other evidence suggesting that CNS metastasis or meningeal metastasis is uncontrolled, as determined by the investigator.
2. Participation in other clinical trials within 4 weeks prior to screening.
3. Receipt of a live attenuated vaccine within 4 weeks prior to screening.
4. Receipt of chemotherapy, targeted therapy, or other experimental drugs within 14 days or at least 5 half-lives (whichever is shorter) prior to screening.
5. Active or uncontrolled infection requiring systemic treatment.
6. Tumor compression of the trachea or major blood vessels, with significant risk as assessed by the investigator.
7. History of any of the following cardiac diseases:

   1. New York Heart Association (NYHA) Class III or IV congestive heart failure.
   2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to screening.
   3. Clinically significant ventricular arrhythmias or unexplained syncope (except those caused by vasovagal or dehydration).
   4. History of severe non-ischemic cardiomyopathy.
8. Active autoimmune disease or other conditions requiring long-term immunosuppressive therapy.
9. History of or concurrent untreated malignancies within 3 years, except for basal cell carcinoma or in situ cervical cancer.
10. Positive for HBsAg or HBcAb with HBV DNA levels above the normal range, HCV antibody positive with HCV RNA levels above the normal range, HIV antibody positive, or positive for syphilis.
11. Pregnant or breastfeeding women.
12. Any other condition that the investigator deems unsuitable for participation in the study.

Where this trial is running

Hangzhou, Zhejiang

• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Fuming Qiu, PhD — Second Affiliated Hospital, School of Medicine, Zhejiang University
• Study coordinator: Fuming Qiu, PhD

Conditions NSCLC; Breast Cancer