MAGE-A4ᶜ¹º³²T for Multi-Tumor

Phase 1Active Not RecruitingNCT03132922

Adaptimmune71 enrolled

Overview

This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Urinary Bladder Cancer Melanoma Head and Neck Cancer Ovarian Cancer Non-Small Cell Lung Cancer

Interventions

Autologous genetically modified MAGE-A4ᶜ¹º³²T cellsGENETIC

Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1

Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiationRADIATION

Up to 10 subjects will be considered for Radiation sub-study. Radiation with an intensity of 1.4Gy for 5 days before infusion of MAGE-A4c1032T cells

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Subject is ≥18 to 75 years of age at the time of signing the study informed consent. 2. Subject has histologically confirmed diagnosis of any one of the indicated tumor types 3. Subject is HLA-A\*02 positive. (This determination will be made under screening protocol ADP-0000-001). 4. Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001). 5. Adequate organ function as indicated in the study protocol 6. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion 7. Subject meets disease-specific requirements per protocol 7\. Subject has anticipated life expectancy \> 6 months prior to leukapheresis and \>3 months prior to lymphodepletion. Exclusion Criteria: 1. Subject does not express appropriate HLA-A genotype 2. Subject is receiving excluded therapy/treatment per protocol 3. Subject has symptomatic CNS metastases. 4. Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness. 5. Subject has active infection with HIV, HBV, HCV or HTLV 6. Subject is pregnant or breastfeeding. Additional Exclusion Criteria for the Radiation Substudy: * Subject does not meet eligibility criteria for the main study (ADP-0044-001). * Subject does not have at least one target lesion amenable to radiation. * Certain radiation therapy within 6 months of clinical trial are an exclusion. * Metastatic disease impinging on the spinal cord or threatening spinal cord compression.

Locations (11)

University of Miami

Miami, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Washington University School of Medicine

St Louis, Missouri, United States

Washington University

St Louis, Missouri, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Duke University Medical Center, Duke Cancer Institute

Durham, North Carolina, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Tennessee Oncology - Sarah Cannon Research Institute

Nashville, Tennessee, United States

M.D. Anderson Cancer Center

Houston, Texas, United States

...and 1 more locations

Outcomes

Primary Outcomes

Number of subjects with adverse events (AE), including serious adverse events (SAEs).

Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.

Time frame: 3.5 years

Determining dose limiting toxicities (DLT) and optimally tolerated dose range

Evaluate DLTs and toxicity assessment using NCI CTCAE.

Time frame: 3.5 years

Evaluation of persistence of genetically modified T cells.

Evaluation of persistence of genetically modified T cells in the periphery.

Time frame: 3.5 years

Measurement of RCL in genetically modified T cells.

Evaluation of RCL in subject PBMCs using PCR-based assay.

Time frame: 3.5 years

Secondary Outcomes

Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).

Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1

Time frame: 3.5 years

Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.

Evaluation of the efficacy of the treatment by assessment of time to first response.

Time frame: 3.5 years

Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.

Evaluation of the efficacy of the treatment by assessment of duration of response.

Time frame: 3.5 years

Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.

Evaluation of the efficacy of the treatment by assessment of duration of stable disease.

Time frame: 3.5 years

Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause

Evaluation of the efficacy of the treatment by assessment of progression-free survival.

Time frame: 3.5 years

Interval between the date of first T cell infusion and date of death due to any cause.

Evaluation of the efficacy of the treatment by assessment of overall survival.

Time frame: 3.5 years

Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)

* New occurrence of any malignancy * New occurrence or exacerbation of a pre-existing neurologic disorder * New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder * New occurrence of a hematologic disorder * New occurrence of any opportunistic and/or serious infections * New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy

Time frame: 15 years post last treatment (infusion)