Overview

This study is a Phase 1 multicenter study with a Dose Escalation and Dose Expansion evaluating safety and efficacy of MT-601 administration to patients with Relapsed or Refractory Lymphoma. The starting dose administered is 200 x 10^6 cells (flat dosing).

Eligibility

Inclusion Criteria:

• All applicable inclusion and exclusion criteria must be met at Screening and at Baseline (re-assessment of eligibility within 14 days prior to group assignment).

        Participants are eligible to be included in the study only if all of the following criteria
        apply and the participant, in the judgement of the Investigator, is an appropriate
        candidate for experimental therapy:
        General:
          1. Participant must be ≥ 18 years of age and capable of giving signed informed consent
             (ICF), which includes compliance with the requirements and restrictions listed in the
             ICF and in the protocol, at the time of signing the ICF.
             Disease Specific:
          2. Cytologically or histologically confirmed diagnosis of NHL, HL or CLL based on the
             2022 World Health Organization (WHO) criteria for hematolymphoid neoplasms
          3. Enrollment of the following subtypes will be eligible:
               1. LBCL including diffuse large B cell lymphoma, primary mediastinal B cell lymphoma
                  (PMBCL), high grade B cell lymphoma (HGBL), T cell rich B cell lymphoma and
                  transformed indolent lymphoma (transformed iNHL)
               2. FL
               3. MCL
               4. MZL
               5. HL
                  The following additional subtypes may be enrolled in disease specific cohorts
                  during Dose Expansion (upon approval by Sponsor)
               6. CLL/SLL
               7. CNS lymphoma
               8. CAR T cell refractory
          4. Must have measurable disease as per 2014 Lugano criteria or 2018 iwCLL criteria.
             Participants with splenic MZL must have measurable splenomegaly on imaging or evidence
             of bone marrow involvement.
             Prior Treatments
          5. Participants who are R/R, are intolerant to, or are considered ineligible for systemic
             standard of care anticancer treatments, including at least 2 prior therapies.
             Participants who refuse standard of care treatments may also be considered if
             documentation is provided that he/she has been made aware of all therapeutic options.
          6. For participants with LBCL, FL, and MCL: Have received CD19-directed CAR T cell
             therapy and relapsed ≥ 30 days or attained an incomplete response as the best response
             within 1 year after CAR T cell administration. Participants who refuse or are
             ineligible for CAR T cell therapy are eligible for this study. Note: during Dose
             Expansion, a specific cohort may be enrolled to evaluate participants who were
             refractory to CD19-directed CAR T cell therapy.
             Health Status
          7. Karnofsky score of ≥70 or performance status of 0 or 1 on the Eastern Cooperative
             Oncology Group (ECOG) scale
          8. Life expectancy ≥12 weeks
          9. Adequate blood, liver, renal and cardiac function:
               1. Hematology: Hemoglobin ≥ 7.0 g/dL (can be transfused), absolute lymphocyte count
                  (ALC) ≥ 300/μL, (prior to apheresis only), absolute neutrophil count (ANC) ≥
                  750/μL and platelet count ≥ 50,000/μL (prior to the conditioning regimen only)
               2. Liver: Bilirubin ≤ 1.5X upper limit of normal (ULN) (exception of bilirubin
                  elevation due to Gilbert's syndrome 3X); aspartate aminotransferase (AST) and
                  alanine aminotransferase (ALT) ≤ 3X ULN
               3. Renal: Serum creatinine ≤ 1.5X ULN or measured or calculated creatinine clearance
                  ≥ 50 mL/min (prior to the conditioning regimen)
               4. Cardiac: left ventricular ejection fraction ≥ 45% (prior to the leukapheresis)
                  Sex
         10. Female: Is a woman of childbearing potential (WOCBP) and using a contraceptive method
             that is highly effective (i.e., with a failure rate of < 1% per year), preferably with
             low user dependency during the intervention period and for at least 6 months after the
             last infusion of MT-601 and agrees not to donate eggs (i.e., ova and oocytes) for the
             purpose of reproduction during this period
         11. Male participants are eligible to participate if they agree to the following during
             the intervention period and for at least 6 months after the last infusion of MT-601:
        Refrain from donating sperm
        PLUS either:
        Be abstinent from intercourse as their preferred and usual lifestyle (abstinent on a
        long-term and persistent basis) and agree to remain abstinent OR Must agree to use a male
        condom AND should also be advised of the benefit for a nonpregnant female partner to use a
        highly effective method of contraception as a condom may break or leak
        Exclusion Criteria:
          -  Patients are excluded from the study if any of the following criteria apply:
        Disease-related
          1. Evidence of bulky disease at the time of the conditioning regimen (≥ 10 cm in diameter
             for LBCL or HL and > 6 cm for other subtypes)
          2. Untreated or ongoing treatment for CNS lymphoma or completed treatment within 2 weeks
             of apheresis (Note: May be allowed in Dose Expansion if disease specific cohort for
             CNS lymphoma is opened)
          3. Refractory to CAR T therapy defined as a best response of stable disease or disease
             progression (Note: May be allowed in Dose Expansion if disease specific cohort for CAR
             T cell therapy refractory is opened)
          4. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or
             blood vessel compression Medical Conditions
          5. Primary immunodeficiency
          6. Severe or uncontrolled autoimmune disorder
          7. History or presence of clinically relevant CNS pathology such as epilepsy, seizure,
             aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar
             disease, organic brain syndrome, or psychosis
          8. Unresolved immune effector cell-associated neurotoxicity syndrome (ICANS) from prior
             CAR T cell administration. Consideration for Grade 1 may be made after discussion with
             the Medical Monitor
          9. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g.,
             cervix, bladder, breast, and/or prostate) unless disease free for at least 3 years
         10. Cardiac conditions:
               1. Medically uncontrolled hypertension (≥ 160 mmHg systolic blood pressure or ≥ 100
                  mmHg diastolic blood pressure)
               2. Congestive heart failure Class ≥ II as defined by the New York Heart Association
               3. Acute coronary syndrome (including unstable angina, coronary artery stenting, or
                  angioplasty, bypass grafting within prior 6 months)
               4. History or evidence of current, uncontrolled, clinically significant, unstable
                  arrhythmias
         11. Oxygen saturation at room air < 92%
         12. Participant has known human immunodeficiency virus (HIV) infection, or active
             hepatitis B virus (HBV)/hepatitis C virus (HCV) infection
         13. Acute bacterial, viral, fungal infection requiring systemic therapy (uncomplicated
             urinary tract infection and bacterial pharyngitis are permitted if responding to
             therapy)
         14. History of severe allergic reactions to any of the study intervention components
             including conditioning regimen, dimethyl sulfoxide (DMSO) or to tocilizumab
         15. Clinically significant reversible toxicities from prior cancer therapy that have not
             recovered to Grade 1 or baseline
               -  Participants with Grade 2 neuropathies due to prior treatment will be allowed on
                  study.
               -  Participants with clinical nonsignificant toxicities, such as alopecia, will be
                  allowed on study.
             Prior/Concomitant Therapy
             Prior to Apheresis:
         16. Receipt of allogeneic hematopoietic cell transplant (HCT) within 12 months; on
             immunosuppression or with evidence of donor/mixed chimera
         17. Receipt of autologous HCT within 3 months
         18. Treatment with CD19-directed CAR T cell therapy within 3 months
         19. Treatment with bispecific antibody within 1 month
         20. Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days
         21. Treatment with monoclonal antibodies impacting T cell function within 14 days
         22. Treatment with systemic immunosuppression including systemic corticosteroids (unless
             ≤5 mg/day oral prednisone or steroid equivalent) within 14 days
         23. Treatment with chemotherapy within 7 days
             Prior to the conditioning regimen:
         24. Treatment with a live, attenuated vaccine within 4 weeks
         25. Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days
         26. Treatment with chemotherapy or biologics/monoclonal antibodies within 14 days
         27. Treatment with radiation therapy within 7 days
         28. Treatment with a tyrosine kinase inhibitor (TKI) within 7 days or 5 half-lives
             (whichever is longer) before conditioning regimen
         29. Hematopoietic growth factors <2 days
             At either time:
         30. Treatment with experimental CAR T cell product unless approved by Medical Monitor
         31. Treatment with other cancer therapy including investigational agents that do not fit
             in the above categories within 14 days
         32. Major surgery within 14 days
             Other
         33. Pregnant or lactating
         34. Any other issue which, in the opinion of the treating physician, would make the
             participant ineligible for the study