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

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])

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).

Study Overview

• Status: Recruiting
• Conditions: Non Hodgkin Lymphoma; Non-Hodgkin Lymphoma, Adult; Non-Hodgkin Lymphoma, Refractory; Non-Hodgkin Lymphoma, Relapsed
• Intervention / Treatment: Drug: MT-601

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gerald Garrett; Phone Number: 713.400.6400; Email: ggarrett@markertherapeutics.com
• Study Contact Backup: Name: Mythili Koneru, MD, PhD; Phone Number: 713.400.6400; Email: mkoneru@markertherapeutics.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Principal Investigator: Geoffrey Shouse, DO, PhD
      • Contact: Geoffrey Shouse, DO, PhD; Phone Number: 626-218-2405; Email: gshouse@coh.org
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute (Sarah Cannon)
      • Contact: Luke Mountjoy, DO; Phone Number: 720-754-4800; Email: Luke.Mountjoy@HealthONEcares.com
      • Principal Investigator: Luke Mountjoy, DO
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology PLLC
      • Contact: Ian Flinn, MD, PhD; Phone Number: 615-329-7274; Email: iflinn@tnonc.com
      • Principal Investigator: Ian Flynn, MD, PhD
  • Texas
    • Austin, Texas, United States, 78704
      • Recruiting
      • Sarah Cannon Research Institute at St. David's South Austin
      • Contact: Aravind Ramakrishnan, MD; Phone Number: 512-816-8600; Email: Aravind.Ramakrishnan@hcahealthcare.com
      • Principal Investigator: Aravind Ramakrishnan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Cytologically or histologically confirmed diagnosis of Non-Hodgkin Lymphoma (in any subtype where CD19+ T cell therapy is approved, e.g., DLBCL, MCL, FL)
2. 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).
3. Patients who have had only BOR of PR to CD19+ CAR T cell therapy may also enroll
4. Are ≥18 years of age prior to administration of MT-601
5. Patients must have patient-derived cells available to make MT-601
6. Karnofsky/Lansky score of ≥70 or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
7. Life expectancy ≥12 weeks

8. Adequate blood, liver, and renal function

   1. Blood: Hemoglobin ≥7.0 g/dL (can be transfused)
   2. Liver: Bilirubin ≤1.5X upper limit of normal (ULN) (exception of bilirubin elevation due to Gilbert's syndrome); aspartate aminotransferase ≤3X ULN
   3. Renal: Serum creatinine ≤2X ULN or measured or calculated creatinine clearance ≥30mL/min
9. 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
10. At least 4 half-lives or 1 week has passed after administration of prior therapy or bridging therapy
11. 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:

  1. Clinically significant or severely symptomatic intercurrent infection (e.g. patients with uncontrolled HIV infection or have active HBV/HCV infection)
  2. Pregnant or lactating
  3. Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study
  4. Taking systemic corticosteroids (exception: physiological doses of steroids allowed)
  5. Autologous or allogeneic HSCT within 1 month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Marker Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Anticipated): February 28, 2028
• Study Completion (Anticipated): February 28, 2028

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: April 4, 2023
• First Posted (Actual): April 5, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Lymphoma; NHL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: MRKR-22-601-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No