MB-105 in Patients With CD5 Positive T-cell Lymphoma

Eligibility 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 willing to undergo biopsy procedure.
• 4. CD5 positivity confirmed by local laboratory using an approved diagnostic test or LDT.
• 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.
• 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 other cancer unless disease-free survival ≥ 2 years (cured non-melanoma skin cancer, in situ breast, non-muscle-invasive bladder or in situ cervical cancer are eligible to enter the trial without time limitations).
• 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).