Efficacy of MT-601 in Patients With Relapsed/Refractory Lymphoma

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

Detailed Description
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This study is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in patients with relapsed or refractory Non-Hodgkin lymphoma (NHL) who either received CD19+ chimeric antigen receptor (CAR) T cell therapy or are ineligible for CD19+ CAR T cell therapy. The study will consist of two portions: 1) Dose Escalation (3+3 design) followed by 2) Dose Expansion. The purpose of the Dose Escalation portion of the study is to test safety and tolerability of higher doses of MT-601 up to 400 x 106 cells. The Dose Expansion portion of this study will begin after completion of the Dose Escalation portion. The purpose of the Dose Expansion portion of the study is to evaluate the clinical efficacy of MT-601 at the dose determined to be safe in the Dose Escalation portion.

Official Title
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A Phase 1 Study of Patient-Derived Multi-Tumor-Associated Antigen-Specific T Cells (MT-601) Administered to Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (NHL [APOLLO])

Conditions
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Non-Hodgkin Lymphoma, Adult, Non-Hodgkin Lymphoma, Refractory, Non-Hodgkin Lymphoma, Relapsed, Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: MT-601


Participation Criteria
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Eligibility Criteria
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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). Patients are eligible to be included in the study only if all of the following criteria apply and the patient, in the judgement of the Investigator, is an appropriate candidate for experimental therapy: Cytologically or histologically confirmed diagnosis of Non-Hodgkin Lymphoma (in any subtype where CD19+ T cell therapy is approved, e.g., DLBCL, MCL, FL) Relapsed or refractory to CD19+ CAR T cell therapy or ineligible for CD19+ CAR T cell therapy (includes patients whose BOR of SD following CD19+ CAR T cell therapy). Patients who have had only BOR of PR to CD19+ CAR T cell therapy may also enroll Are ≥18 years of age prior to administration of MT-601 Patients must have patient-derived cells available to make MT-601 Karnofsky/Lansky score of ≥70 or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Life expectancy ≥12 weeks Adequate blood, liver, and renal function Blood: Hemoglobin ≥7.0 g/dL (can be transfused) Liver: Bilirubin ≤1.5X upper limit of normal (ULN) (exception of bilirubin elevation due to Gilbert's syndrome); aspartate aminotransferase ≤3X ULN Renal: Serum creatinine ≤2X ULN or measured or calculated creatinine clearance ≥30mL/min Sexually active patients must be willing to utilize one of the highly effective birth control methods or practice complete abstinence starting from Screening for T cell infusion until 6 months after the last T cell infusion. Male patients who are sexually active must agree to use a condom during this period At least 4 half-lives or 1 week has passed after administration of prior therapy or bridging therapy Dose escalation defined as patients whose prior treatment course does not meet precise eligibility criteria but may still be approved upon review by the Sponsor Exclusion Criteria: Patients are excluded from the study if any of the following criteria apply: Clinically significant or severely symptomatic intercurrent infection (e.g. patients with uncontrolled HIV infection or have active HBV/HCV infection) Pregnant or lactating Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study Taking systemic corticosteroids (exception: physiological doses of steroids allowed) Autologous or allogeneic HSCT within 1 month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm Study<br>Single arm study evaluating MT-601 investigational product at 200 million cells and 400 million cells per dose | Drug: MT-601<br>* Multi-antigen specific CD4+ andCD8+ T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation | To assess safety and tolerability of escalating doses of MT-601 by the number of participants with MT-601 Dose Limiting Toxicities (DLTs) and Safety events (including but not limited to): treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), deaths, and clinical laboratory abnormalities per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) | After 3 or 6 patients in each dose cohort have been treated with MT-601 and have had the opportunity to be followed for 28 days. | 
| Dose Expansion (ORR) | To assess anti-tumor activity of MT-601 based on Lugano Classification by the following endpoints: Objective response rate (ORR) defined as the proportion of treated patients who achieve a best response of complete remission (CR) or partial response (PR) per Lugano Classification. The Clopper-Pearson method will be used to estimate the two-sided exact 95% confidence interval for ORR. | 12 months after the last patient treated in the Dose Expansion portion of the study receiving the first dose of MT-601. | 
| Dose Expansion (DOR) | To assess anti-tumor activity of MT-601 based on Lugano Classification by the following endpoints: Duration of response (DOR) defined for patients who attain a best response of CR or PR and is the time between the date of first documented CR or PR and the date of the first observed progression per Lugano Classification. DOR will be estimated using the Kaplan-Meier (KM) product limit method. The median DOR and corresponding 95% confidence intervals (CI) will be estimated. | 12 months after the last patient treated in the Dose Expansion portion of the study receiving the first dose of MT-601. | 
| Dose Expansion (CR) | To assess anti-tumor activity of MT-601 based on Lugano Classification by the following endpoints: Complete remission (CR) rate defined as the proportion of treated patients who achieve a best response of CR per Lugano Classification. The Clopper-Pearson method will be used to estimate the two-sided exact 95% confidence interval for CR rate estimates. | 12 months after the last patient treated in the Dose Expansion portion of the study receiving the first dose of MT-601. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Lymphoma