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

Inclusion Criteria

• Male or female ≥ 18 years of age.
• Patients with r/r TCL per WHO 2022 criteria.
• r/r CTCL that has failed ≥ 2 prior lines of standard of care (SoC) therapy.
• r/r PTCL that has failed ≥ 1 prior lines of SoC therapy. Note: patients with CD30+ disease should have received brentuximab vedotin.
• Has available tumor tissue or is willing to undergo a biopsy procedure.
• 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%.
• Karnofsky performance score ≥ 70% or higher.
• Prior CAR T-cell therapy must have occurred > 60 days prior to study enrollment and must have no evidence of CAR persistence.
• Measurable or detectable disease
• PTCL per Lugano criteria
• CTCL per Global (ISCL/EORTC/USCCL) criteria.
• Prior autologous or allogenic hematopoietic stem cell transplant (HSCT) must have occurred more than 60 days prior to study enrollment.
• Adequate bone marrow function defined as:
• Absolute neutrophil count (ANC) ≥ 1500/μL (≥ 1000/μL for patients with prior HSCT or marrow involvement)
• Absolute lymphocyte count ≥200 cells/μL
• Hemoglobin ≥ 8 g/dL (transfusion permitted)
• Platelet count ≥ 75 000/μL (≥50 000/μL for patients with marrow involvement).
• Organ function as follows:
• Cardiac: left ventricular ejection fraction (LVEF) ≥ 50% by Echo or radionuclide scan.
• Pulmonary: oxygen saturation ≥ 92% (room air).
• Renal: calculated creatinine clearance > 30 mL/min.
• 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.
• 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).
• 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

• 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.
• Contraindication to leukapheresis.
• Prior treatment with any CD5-targeted therapy.
• Any evidence of the following active viral infections:
• HIV infection.
• 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).
• Hepatitis C (HCV) infection with detectable viral load. Patients cured of HCV may be enrolled.
• 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.
• 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.
• History of hypersensitivity reactions to products containing murine proteins.
• Active CNS lymphoma.
• 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.
• Patients who have received systemic immunosuppressive therapy for treatment of GVHD within 28 days of leukapheresis.
• 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.
• Patients who have received donor lymphocyte infusions within 28 days of MB-105 infusion.
• Comorbidity that would impair the patient's ability to receive or tolerate MB-105 and/or affect participation in the study:
• 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.
• History of central nervous system (CNS) disorder(s) such as an uncontrolled seizure disorder, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• 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.
• 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.
• 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.
• Received bendamustine prior to enrollment (unless received an allo-HSCT in the interim).