Treatment for CD5 Positive T-cell Lymphoma using MB-105

A Phase 2, Open-label, Multicenter Study of MB-105 in Patients With CD5 Positive (CD5+) Relapsed / Refractory T-cell Lymphoma (r/r TCL).

This study is testing a new treatment called MB-105 to see if it can help people with CD5 positive T-cell lymphoma that hasn't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: March Biosciences Inc (Industry-sponsored)
• Drugs / interventions: brentuximab, CAR T, prednisone, Chimeric antigen receptor
• Locations: 12 sites (San Diego, California and 11 other locations)
• Trial ID: NCT06534060 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial evaluates the safety and efficacy of MB-105 in patients with CD5 Positive relapsed or refractory T-cell lymphoma. The study employs a Simon two-stage design, initially enrolling 15 patients to assess the recommended phase 2 dose (RP2D) of MB-105. After the first 6 patients receive treatment and complete safety evaluations, the Independent Data Monitoring Committee will determine if the study can proceed with additional patients based on safety data. The goal is to estimate the response rate of the treatment according to established lymphoma criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with CD5 Positive relapsed or refractory T-cell lymphoma who have failed previous standard therapies.

Not a fit: Patients with T-cell lymphoma who have not undergone prior therapies or those with CD5 negative tumors 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 T-cell lymphoma.

How similar studies have performed: While this approach is novel for CD5 Positive T-cell lymphoma, similar CAR T-cell therapies have shown promise in other types of lymphomas.

Eligibility criteria

Inclusion Criteria:

1. Male or female ≥ 18 years of age.
2. Patients with r/r TCL per WHO 2022 criteria.

   1. r/r CTCL that has failed ≥ 2 prior lines of standard of care (SoC) therapy.
   2. r/r PTCL that has failed ≥ 1 prior lines of SoC therapy. Note: patients with CD30+ disease should have received brentuximab vedotin.
3. Has available tumor tissue or is willing to undergo a biopsy procedure.
4. CD5 positivity confirmed by local laboratory using an approved diagnostic test or LDT. CD5 positivity is currently defined as having ≥ 50% CD5 expression. An exploratory cohort will enroll patients with CD5 expression below 50%.
5. Karnofsky performance score ≥ 70% or higher.
6. Prior CAR T-cell therapy must have occurred \> 60 days prior to study enrollment and must have no evidence of CAR persistence.
7. Measurable or detectable disease

   1. PTCL per Lugano criteria
   2. CTCL per Global (ISCL/EORTC/USCCL) criteria.
8. Prior autologous or allogenic hematopoietic stem cell transplant (HSCT) must have occurred more than 60 days prior to study enrollment.
9. Adequate bone marrow function defined as:

   1. Absolute neutrophil count (ANC) ≥ 1500/μL (≥ 1000/μL for patients with prior HSCT or marrow involvement)
   2. Absolute lymphocyte count ≥200 cells/μL
   3. Hemoglobin ≥ 8 g/dL (transfusion permitted)
   4. Platelet count ≥ 75 000/μL (≥50 000/μL for patients with marrow involvement).
10. Organ function as follows:

    1. Cardiac: left ventricular ejection fraction (LVEF) ≥ 50% by Echo or radionuclide scan.
    2. Pulmonary: oxygen saturation ≥ 92% (room air).
    3. Renal: calculated creatinine clearance \> 30 mL/min.
    4. Liver:

       * Total bilirubin \< 1.5 x ULN (\< 2 × upper limit of normal (ULN)) if liver involvement).
       * If no liver involvement and total bilirubin ≥1.5 x ≤ ULN, direct bilirubin \< ULN (Gilbert syndrome)
       * Aspartate aminotransferase / alanine aminotransferase \< 3 × ULN (5 x ULN if liver involvement).
       * Albumin \> 2.5 g/dL.
11. For females of childbearing potential (defined as \< 24 months of amenorrhea or not surgically sterile \[absence of ovaries and/or uterus\]), a negative serum pregnancy test must be documented at screening, and prior to lymphodepletion (conditioning).
12. For females of childbearing potential and males, a highly effective method of contraception together with a barrier method must be used from the start of lymphodepletion (conditioning) and for at least 12 months after the last dose of study agent.

Exclusion Criteria:

1. Sezary syndrome. For other tumor types, if there is a suspicion of significant circulating disease at time of leukapheresis, discuss eligibility with medical monitor prior to proceeding.
2. Contraindication to leukapheresis.
3. Prior treatment with any CD5-targeted therapy.
4. Any evidence of the following active viral infections:

   1. HIV infection.
   2. Chronic hepatitis B virus (cHBV) infection with detectable viral load. Patients with cHBV, who are receiving anti-viral prophylaxis, may be enrolled if they are asymptomatic for \>5 days prior to signing informed consent (ICF).
   3. Hepatitis C (HCV) infection with detectable viral load. Patients cured of HCV may be enrolled.
5. Presence of any active, uncontrolled systemic bacterial, viral or fungal infection requiring intravenous (IV) anti-infectives, including clinically significant viral infection or uncontrolled viral reactivation of Epstein-Barr virus, Cytomegalovirus, Adenovirus, BK-virus, or Human herpesvirus 6. If treated with anti-infective agents, patients must be asymptomatic for \>5 days prior to enrollment.
6. History of any malignancy within 2 years with the exception of cured stage 1 cancers or CIS and potentially indolent cancers not requiring active treatment or controlled with hormone therapy. Discuss patients with indolent cancers with the medical monitor.
7. History of hypersensitivity reactions to products containing murine proteins.
8. Active CNS lymphoma.
9. Evidence of acute graft versus host disease (aGVHD) \> Grade 2 Mount Sinai Acute GVHD International Consortium (MAGIC) or chronic GVHD \> mild (NIH) requiring ongoing systemic steroids and/or multiagent therapy.
10. Patients who have received systemic immunosuppressive therapy for treatment of GVHD within 28 days of leukapheresis.
11. Currently requiring systemic corticosteroid therapy (10 mg/day or less of prednisone or equivalent doses of other systemic steroids are allowed for control of non-exclusionary pre-existing conditions). A 2-week washout is required prior to leukapheresis and prior to lymphodepletion for patients on \> 10 mg/day prednisone equivalent.
12. Patients who have received donor lymphocyte infusions within 28 days of MB-105 infusion.
13. Comorbidity that would impair the patient's ability to receive or tolerate MB-105 and/or affect participation in the study:

    1. History of cardio- or cerebrovascular disease including myocardial infarction, unstable angina, or congestive heart failure (NYHA class III-IV) within 6 months or cerebrovascular accident (CVA; stroke) within 12 months prior to informed consent.
    2. History of central nervous system (CNS) disorder(s) such as an uncontrolled seizure disorder, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
    3. Any serious underlying medical or psychiatric condition deemed by the investigator and medical monitor to be exclusionary due to risk to the patient or to protocol compliance.
14. History of autoimmune disorders, including rheumatic diseases and thyroid disorders (though patients with a history of thyroid disease who have undergone successful therapy may be suitable). Exemptions for mild or limited disease may be granted after discussion between the Investigator and sponsor's medical monitor.
15. Participated in active treatment on other interventional research clinical trials \< 30 days before enrollment (participation in follow-up permitted). Contact the medical monitor to discuss prior experimental agents targeting the T cell lineage and the appropriate washout period.
16. Received bendamustine prior to enrollment (unless received an allo-HSCT in the interim).

Where this trial is running

San Diego, California and 11 other locations

• University of San Diego (UCSD)-Moores Cancer Center — San Diego, California, United States (Recruiting)
• SCRI - Colorado Blood Cancer Institute (CBCI) — Denver, Colorado, United States (Not_yet_recruiting)
• Moffitt Cancer Center Magnolia Campus — Tampa, Florida, United States (Recruiting)
• University of Iowa — Iowa City, Iowa, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• University of Nebraska — Omaha, Nebraska, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Not_yet_recruiting)
• Oregan Health & Science University — Portland, Oregon, United States (Not_yet_recruiting)
• Baylor College of Medicine — Houston, Texas, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Federica Giordano, Ph.D.

Conditions Lymphoma, T-Cell; MB-105-201