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

Clinical Study of CEA-Targeted Chimeric Antigen Receptor T Lymphocytes (CAR-T) in Advanced CEA-Positive Malignant Solid Tumors

This trial will try CEA-targeted CAR-T cell infusions in adults with advanced CEA-positive cancers (such as colorectal, gastric, esophageal, lung, or pancreatic cancer) to see if the treatment is safe and helps control the disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Hefei, Anhui)
• Trial ID: NCT07179692 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase 1 trial using a dose-escalation (Part A) followed by dose-expansion (Part B) design to define a recommended dose and schedule of CEA-targeted CAR-T cells. Patients are allocated to one of three parallel infusion-route cohorts: intravenous, intrapleural, or intraperitoneal administration. Part A will enroll 3–6 subjects per dose level to identify the recommended dose, and Part B will treat additional subjects at that dose to gather more safety and preliminary efficacy data. The study will monitor safety, pharmacokinetics/persistence of CAR-T cells, and early antitumor activity by RECIST criteria.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed advanced, metastatic, or recurrent CEA-positive solid tumors who have failed at least second-line standard treatments, have ECOG 0–2, measurable disease per RECIST 1.1, and tumor CEA membrane staining ≥10% (or serum CEA >10 µg/L if IHC is older than 3 months) are the intended candidates.

Not a fit: Patients whose tumors lack CEA expression, who have poor organ function or uncontrolled comorbidities, who have an expected survival <12 weeks, or who have severe psychiatric disorders are unlikely to benefit from this experimental therapy.

Why it matters

Potential benefit: If successful, this targeted CAR-T approach could offer a new treatment option that reduces or controls CEA-positive tumors for patients who have exhausted standard therapies.

How similar studies have performed: CEA-targeted CAR-T in solid tumors remains largely experimental; a few early-phase trials have reported limited signals of activity but no definitive, widely replicated success to date.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years, no gender restriction;
2. Histopathologically confirmed diagnosis of advanced, metastatic, or recurrent malignant tumors, primarily including colorectal cancer, esophageal cancer, gastric cancer, pancreatic cancer, lung cancer, and cholangiocarcinoma;
3. Failure of at least second-line standard treatment (disease progression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack of effective treatment options;
4. Immunohistochemical staining of tumor samples showing CEA positivity (clear membrane staining, positivity rate ≥ 10%) within the past 3 months; if the immunohistochemical result is older than 3 months (clear membrane staining, positivity rate ≥ 10%), serum CEA must exceed 10 µg/L;
5. At least one evaluable lesion according to RECIST 1.1 criteria;
6. ECOG performance status of 0-2;
7. Expected survival of ≥ 12 weeks;
8. No severe psychiatric disorders;
9. Unless otherwise specified, the following important organ function criteria must be met:

   1. Hematology: White blood cells \> 2.0 × 10\^9/L, neutrophils \> 0.8 × 10\^9/L, lymphocytes \> 0.5 × 10\^9/L, platelets \> 50 × 10\^9/L, hemoglobin \> 90 g/L;
   2. Cardiac function: Echocardiogram shows ejection fraction ≥ 50%, ECG shows no significant abnormalities;
   3. Renal function: Serum creatinine ≤ 2.0 × ULN;
   4. Liver function: ALT and AST ≤ 3.0 × ULN (can be relaxed to ≤ 5.0 × ULN for patients with liver tumor infiltration);
   5. Total bilirubin ≤ 2.0 × ULN;
   6. Oxygen saturation \> 92% without supplemental oxygen;
10. Eligible for single or venous blood collection, and no contraindications for cell collection;
11. The subject agrees to use reliable and effective contraception methods from the time of signing the informed consent form until 1 year after CAR-T cell infusion (excluding rhythm method);
12. The subject or their authorized guardian agrees to participate in this clinical trial and signs the informed consent form (ICF), indicating understanding of the trial's purpose and procedures and willingness to participate in the study.

Exclusion Criteria:

1. Clinically symptomatic central nervous system metastasis or meningeal metastasis at screening, or other evidence indicating that central nervous system or meningeal metastasis has not been controlled, as determined by the investigator, making the patient unsuitable for enrollment.
2. Participation in another clinical trial within 1 month prior to screening.
3. Receipt of live attenuated vaccines within 4 weeks prior to screening.
4. Received the following anti-tumor treatments within 14 days or at least 5 half-lives (whichever is shorter) prior to screening: chemotherapy, targeted therapy, or other experimental drug treatments.
5. Active infection requiring systemic treatment or an uncontrolled infection.
6. Bowel obstruction, active gastrointestinal bleeding, or a history of major gastrointestinal bleeding within the last 3 months, or severe gastrointestinal conditions such as severe gastric or duodenal ulcers, severe ulcerative colitis, or other severe gastrointestinal inflammations.
7. Toxicity from prior anti-tumor treatments has not improved to baseline levels or ≤ grade 1, except for alopecia or peripheral neuropathy.
8. Any of the following cardiac conditions:

   1. New York Heart Association (NYHA) Class III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to enrollment;
   3. Clinically significant ventricular arrhythmias, or history of unexplained syncope (excluding cases due to vasovagal or dehydration);
   4. Severe non-ischemic cardiomyopathy.
9. Active autoimmune diseases or other conditions requiring long-term use of immunosuppressive therapy.
10. History of another malignancy within the past 3 years, excluding treated and stable in situ cervical cancer or basal cell carcinoma of the skin.
11. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA levels above the normal range; positive for hepatitis C virus (HCV) antibodies with peripheral blood HCV RNA levels above the normal range; positive for HIV antibodies; or positive for syphilis testing.
12. Pregnant or breastfeeding women.
13. Any other conditions that, in the opinion of the investigator, make the patient unsuitable for participation in the study.

Where this trial is running

Hefei, Anhui

• The 901 Hospital of Joint Logistics Support Force of People Liberation Army — Hefei, Anhui, China (Recruiting)

Study contacts

• Principal investigator: Donglai Lv, MD — The 901 Hospital of Joint Logistics Support Force of People Liberation Army
• Study coordinator: Donglai Lv, MD

Conditions Lung Cancer; Gastric Cancer; Colon Cancer; Rectal Cancer; Esophageal Cancer; Pancreas Cancer