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Active, Not Recruiting

NCT Number: NCT03132922

MAGE-A4ᶜ¹º³²T for Multi-Tumor

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Urinary Bladder Cancer Adenocarcinoma Adnexal Diseases Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Cancer Esophageal Diseases Esophageal Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastric Cancer Gastroesophageal Junction Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Cancer Head and Neck Neoplasms Liposarcoma Liposarcoma, Myxoid Lung Diseases Lung Neoplasms Male Urogenital Diseases Melanoma Myxoid Round Cell Liposarcoma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Adipose Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplastic Processes Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-small Cell Lung Cancer Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Sarcoma, Synovial Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Stomach Diseases Stomach Neoplasms Synovial Sarcoma Thoracic Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subject is ≥18 to 75 years of age at the time of signing the study informed consent.
  • Subject has histologically confirmed diagnosis of any one of the indicated tumor types
  • Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).
  • Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).
  • Adequate organ function as indicated in the study protocol
  • Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
  • Subject meets disease-specific requirements per protocol
  • Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.

Exclusion criteria

  • Subject does not express appropriate HLA-A genotype
  • Subject is receiving excluded therapy/treatment per protocol
  • Subject has symptomatic CNS metastases.
  • Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.
  • Subject has active infection with HIV, HBV, HCV or HTLV
  • 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.

Treatment and study plan

Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

Genetic

Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1

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

Radiation

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

Primary outcomes

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

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

    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.

  2. Peak Persistence

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

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

  3. Replication Competent Lentivirus (RCL)

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

    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.

Secondary outcomes

  1. Overall Response Rate (ORR)

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

    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.

  2. Best Overall Response (BOR)

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

    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)

  3. Time to Response (TTR)

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

    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.

  4. Duration of Response (DoR)

    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).

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

  5. Duration of Stable Disease (DoSD)

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

    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.

  6. Progression Free Survival (PFS)

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

    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.

  7. Overall Survival (OS)

    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

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

Sponsors and collaborators

Lead sponsor

USWM CT, LLC

Industry

Registry information

Official study title

Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors

Important dates

Study start
2017
Primary completion
2022
Study completion
2032
First posted
Apr 28, 2017
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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