BAFFR-targeting CAR T cells for relapsed or refractory B-cell lymphoma

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

This study is testing a new type of CAR T cell therapy that targets a specific protein on cancer cells to see if it can help people with B-cell lymphoma that has come back or didn’t respond to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: PeproMene Bio, Inc. (Industry-sponsored)
• Drugs / interventions: CAR T, CAR-T
• Locations: 6 sites (Duarte, California and 5 other locations)
• Trial ID: NCT05370430 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial evaluates the safety and optimal dosage of BAFFR-targeting CAR T cells in patients with relapsed or refractory B-cell Non-Hodgkin's Lymphoma (B-NHL). The study involves collecting T cells from the patient and genetically modifying them to recognize BAFFR, a protein found on cancer cells. The modified T cells are then reintroduced into the patient to enhance the immune response against the cancer. The trial aims to determine the effectiveness of this approach in treating patients whose lymphoma has returned or is resistant to previous therapies.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed relapsed or refractory B-cell Non-Hodgkin's Lymphoma expressing BAFF-R.

Not a fit: Patients with B-NHL that does not express BAFF-R or those with significant comorbidities affecting treatment eligibility may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell Non-Hodgkin's Lymphoma.

How similar studies have performed: While CAR T cell therapies have shown success in treating various hematological malignancies, this specific approach targeting BAFFR is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Informed Consent: Signed informed consent by the participant or legally authorized representative.
2. Age \& Performance Status:

   * Age ≥ 18 years
   * ECOG performance status ≤ 2
3. Diagnosis \& Disease Criteria:

   * Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
   * BAFF-R expression on lymphoma cells required.
4. Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
5. Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence \< 5% before leukapheresis.
6. Organ Function \& Laboratory Criteria:

   * Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
   * Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT \< 3x ULN.
   * Renal Function: CrCl ≥ 50 mL/min.
   * Cardiac \& Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation \> 91% on room air.
7. Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
8. Reproductive Considerations:

   * Negative pregnancy test for females of childbearing potential.
   * Use of effective contraception or abstinence through 3 months post-treatment.

Exclusion Criteria:

1. Prior Therapies \& Transplants:

   * Prior allogeneic SCT.
   * Autologous SCT \< 6 months before leukapheresis.
   * Concurrent systemic steroids or chronic immunosuppressant use.
2. Disease-Specific Exclusions:

   * Cardiac lymphoma involvement.
   * Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
3. Medical Conditions:

   * Active autoimmune disease requiring immunosuppressants.
   * Primary immunodeficiency.
   * Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
   * Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
   * History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
   * Uncontrolled systemic infections or active CNS lymphoma.
4. Pregnancy \& Breastfeeding: Females who are pregnant or nursing.
5. Other Considerations:

   * Investigator-determined safety concerns.
   * Potential noncompliance with study procedures.

Where this trial is running

Duarte, California and 5 other locations

• City of Hope Medical Center — Duarte, California, United States (Recruiting)
• Stanford University — Stanford, California, United States (Recruiting)
• University of Kansas Hospital — Kansas City, Kansas, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Atrium Health Levine Cancer Institute - Morehead — Charlotte, North Carolina, United States (Recruiting)
• Providence Swedish Cancer Institute — Seattle, Washington, United States (Recruiting)

Study contacts

• Study coordinator: Hazel (Ting-Ying) Cheng, PhD

Conditions Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma; Relapsed or Refractory; Mantle Cell Lymphoma; BAFFR-CAR T cells; B-cell Non-Hodgkin's Lymphoma; B-NHL; BAFFR; MCL