GP350 CAR-T for relapsed or EBV-associated lymphoid neoplasms

GP350 CAR-T Cells for Relapse/Refractory and Epstein-Barr Virus Infection Associated Lymphoid Neoplasms, an Open-label, Single-arm Clinical Trial

This trial will try GP350 CAR-T cell therapy in people with relapsed or refractory lymphoid cancers that are linked to Epstein-Barr virus.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: The Second Hospital of Anhui Medical University (Academic / other)
• Drugs / interventions: prednisone, CAR-T, CAR T, chemotherapy
• Locations: 1 site (Hefei, Anhui)
• Trial ID: NCT07306156 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm Phase 1/2 study testing GP350-directed CAR-T cells in patients with relapsed/refractory or EBV-associated lymphoid neoplasms. Participants undergo leukapheresis to collect immune cells, receive conditioning chemotherapy, and then get an intravenous infusion of the engineered CAR-T cells. Safety, tolerability, and early signs of anti-tumor activity will be monitored during a post-treatment assessment and through long-term follow-up. The trial is conducted at a single clinical site in Hefei, Anhui, China.

Who should consider this trial

Good fit: Ideal candidates are adults with a confirmed lymphoid neoplasm (per WHO-HAEM5) that is relapsed or refractory or meets the study's criteria for EBV association (high EBV DNA load, GP350+ tumor cells, or supportive serology).

Not a fit: Patients without evidence of EBV involvement, those who cannot tolerate leukapheresis or conditioning chemotherapy, or those with medical conditions that preclude CAR-T infusion are unlikely to benefit.

Why it matters

Potential benefit: If successful, GP350 CAR-T could produce durable remissions for patients with EBV-associated relapsed lymphoid neoplasms who have few other options.

How similar studies have performed: While CD19-directed CAR-Ts have shown strong results in some B-cell lymphomas, GP350-targeted CAR-T for EBV-driven lymphoid neoplasms is a novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis: Confirmed diagnosis of lymphoid neoplasms according to WHO-HAEM5 (Alaggio R. et al. doi:10.1038/s41375-022-01620-2);
2. Disease Assessment:

   1. Criteria for Relapsed/Refractory lymphoid neoplasms: Meeting any one of the following three conditions: ① Failure to achieve at least a partial response (PR) per Lugano criteria after two cycles of standard first-line therapy; ② Disease progression within six months after achieving a response to first-line therapy, or progression after six months with no response to the original first-line or second-line regimen; ③ Relapse after hematopoietic stem cell transplantation.
   2. Criteria for EBV Infection: Meeting any one of the following three conditions: ① Peripheral blood (plasma or whole blood) EBV DNA load ≥ 10³ copies/ml by quantitative PCR; ②Tumor cell GP350 positivity (≥10% of tumor cells by immunohistochemistry or flow cytometry); ③ Serological detection of EBV antibodies indicating any of the following: positive anti-VCA-IgM; positive anti-EA-IgG; or simultaneous positivity for anti-VCA-IgM, anti-VCA-IgG, and anti-EBNA-IgG.
   3. At least one evaluable lymphoma lesion according to Lugano criteria, or confirmed active lytic EBV infection.
3. Performance Status: ECOG score 0-2 and expected survival ≥3 months;
4. Age: 18-70 years, regardless of sex;
5. Hematologic Criteria:

   * Absolute neutrophil count (ANC) ≥1.0×10⁹/L;
   * Hemoglobin \>60 g/L;
   * CD3+ T-cell count \>0.5×10⁹/L;
   * Platelet count \>30×10⁹/L;
6. Organ Function:

   * Creatinine clearance ≥60 mL/min;
   * ALT/AST ≤2× upper limit of normal (ULN);
   * Total bilirubin ≤2× ULN;
   * Left ventricular ejection fraction (LVEF) ≥50%, no pericardial effusion, and no clinically significant ECG abnormalities;
   * Minimal or no pleural/ascitic fluid;
   * Oxygen saturation ≥95%;
7. Contraception:

   * Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception until the last follow-up;
   * Male participants with fertile partners must agree to use effective contraception until the last follow-up;
8. Informed Consent: Psychologically stable, capable of understanding the study's purpose and procedures, willing to participate voluntarily, and able to provide signed informed consent and comply with protocol requirements.

Exclusion Criteria:

1. Active Infections: Presence of active hepatitis A, B, or C infection, or other uncontrolled severe active infections (excluding EBV infection);
2. Immunosuppression:

   * History of acquired immunodeficiency syndrome (AIDS);
   * Chronic use of immunosuppressants (including corticosteroids at doses equivalent to \>15 mg/day of prednisone) for other conditions;
3. Cardiac Dysfunction:

   1. NYHA Class III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass grafting within the past 6 months;
   3. Clinically significant ventricular arrhythmia or unexplained syncope;
   4. History of severe non-ischemic cardiomyopathy;
   5. Cardiac insufficiency (left ventricular ejection fraction \<45%) within 8 weeks prior to apheresis;
4. Pregnancy/Contraception:

   * Pregnant or lactating women;
   * Participants (male or female) unwilling to use contraception;
5. Hepatic/Renal Impairment:

   * AST/ALT \>3× upper limit of normal (ULN);
   * Total bilirubin \>3× ULN;
   * Creatinine clearance \<60 mL/min;
6. Allergies: History of severe hypersensitivity to any study drugs;
7. Prior Stem Cell Transplant: Must have discontinued immunosuppressants for \>6 weeks post-transplant with no signs of graft-versus-host disease (GVHD);
8. Other Exclusionary Conditions: Any other condition deemed unsuitable by the investigator (e.g., coagulation disorders, hemolytic anemia, etc.).

Where this trial is running

Hefei, Anhui

• The Second Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (Recruiting)

Study contacts

• Study coordinator: Zhimin Zhai, MD

Conditions EBV Associated Lymphoid Neoplasms; LAHS; EBV; Lymphoma; Lymphoid neoplasms; CAR-T