MAGE-A4ᶜ¹º³²T for Multi-Tumor

Phase 1Active Not RecruitingNCT03132922

USWM CT, LLC71 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

Adverse Events (AE) Including Serious Adverse Events (SAE)

An AE was defined as any untoward medical occurrence in a clinical study participant who received a pharmaceutical product, regardless of causality. An AE was , therefore, any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with AEs (including SAEs) are presented.

Time frame: From the start of lymphodepleting chemotherapy until end of interventional phase (up to 3.2 years).

Peak Persistence

Peak persistence of afamitresgene autoleucel cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC).

Time frame: From afamitresgene autoleucel infusion up to 18 months post-infusion

Replication Competent Lentivirus (RCL)

The presence of RCL was assessed by quantitative polymerase chain reaction (qPCR) targeting a segment of the vesicular stomatitis virus glycoprotein (VSV-G) coding sequence.

Time frame: From afamitresgene autoleucel infusion to 3 months post-infusion

Secondary Outcomes

Overall Response Rate (ORR)

ORR, defined as the proportion of participants with Best Overall Response (BOR) of confirmed completed response (CR) or partial response (PR) among participants with measurable disease at Baseline. The ORR was based on the assessment of response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by local radiologist. Participants with unknown or missing response were treated as non-responders.

Time frame: From afamitresgene autoleucel infusion until disease progression/recurrence (up to 3.2 years)

Best Overall Response (BOR)

BOR was defined as the best response recorded from the date of T-cell infusion until disease progression. Response categories from best to worst were, confirmed CR, confirmed PR, stable disease (SD), progressive disease (PD), and not evaluable (NE) (per RECIST v1.1)

Time frame: From afamitresgene autoleucel infusion until disease progression/recurrence (up to 3.2 years)

Time to Response (TTR)

TTR was defined as the interval between the date of the first T-cell infusion and the earliest date of the first documented confirmed CR or confirmed PR.

Time frame: From afamitresgene autoleucel infusion until first documented confirmed CR or PR

Duration of Response (DoR)

DoR was measured from the first CR/PR (whichever was first recorded) until the first date of progressive disease.

Time frame: From initial confirmed response (DR or PR) until PD or censored date. is defined as all participants who had not experienced the event of interest (i.e. ongoing, event free) at the time of the data cut off (used for the analysis).

Duration of Stable Disease (DoSD)

DoSD was defined as the time from the date of T-cell infusion to the first date of the radiological PD. This analysis of DoSD only applied to participants with BOR as confirmed CR, confirmed PR, or confirmed SD.

Time frame: From date of afamitresgene autoleucel infusion to first date of radiological PD or censored date

Progression Free Survival (PFS)

PFS was defined as the time from the date of the first T-cell infusion to the first date of the radiological PD or death date (due to any reason), whichever event was earlier.

Time frame: From afamitresgene autoleucel infusion until first documented PD or death due to any cause, whichever comes first, or censored date.

Overall Survival (OS)

OS was defined as the time from the date of afamitresgene autoleucel infusion to the date of death (due to any reason).

Time frame: From afamitresgene autoleucel infusion until death due to any reason or censored date From afamitresgene autoleucel infusion until death due to any reason or censored date