MAGE-A4ᶜ¹º³²T for Multi-Tumor

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

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 Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Head and Neck Cancer; Gastric Cancer; Esophageal Cancer; Ovarian Cancer; Non-Small Cell Lung Cancer; Urinary Bladder Cancer; Synovial Sarcoma; Gastroesophageal Junction; Myxoid Round Cell Liposarcoma
• Intervention / Treatment: Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells; Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X6
      • Princess Margaret Cancer Centre
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63112
      • Washington University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center, Duke Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells	Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells; Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1
Experimental: Radiation Sub-Study: Autologous genetically modified MAGE-A4c1	Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	From afamitresgene autoleucel infusion to 3 months post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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.	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.	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.	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.	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).	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAGE-A4c1032T cell trafficking in tumor lesion(s).	Evaluation of post-infusion T-cell trafficking in irradiated vs non-irradiation lesions	3.5 years

Collaborators and Investigators

• Sponsor: USWM CT, LLC
• Investigators: Principal Investigator: David Hong, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Sanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020.
• Hong DS, Van Tine BA, Biswas S, McAlpine C, Johnson ML, Olszanski AJ, Clarke JM, Araujo D, Blumenschein GR Jr, Kebriaei P, Lin Q, Tipping AJ, Sanderson JP, Wang R, Trivedi T, Annareddy T, Bai J, Rafail S, Sun A, Fernandes L, Navenot JM, Bushman FD, Everett JK, Karadeniz D, Broad R, Isabelle M, Naidoo R, Bath N, Betts G, Wolchinsky Z, Batrakou DG, Van Winkle E, Elefant E, Ghobadi A, Cashen A, Grand'Maison A, McCarthy P, Fracasso PM, Norry E, Williams D, Druta M, Liebner DA, Odunsi K, Butler MO. Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial. Nat Med. 2023 Jan;29(1):104-114. doi: 10.1038/s41591-022-02128-z. Epub 2023 Jan 9.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2017
• Primary Completion (Actual): December 27, 2022
• Study Completion (Estimated): September 1, 2032

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Metastatic; Melanoma; Bladder; Radiation therapy; Sarcoma; Urothelial Cancer; Immuno-oncology; Ovarian; T Cell Therapy; T Cell Receptor; SPEAR T Cell; MAGE-A4; Previously Treated; Squamous, adenosquamous, adenocarcinoma or large cell NSCLC; Squamous or adenocarcinoma esophageal cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Esophageal Diseases; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Nevi and Melanomas; Skin Neoplasms; Urinary Bladder Diseases; Neoplasms, Adipose Tissue; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Liposarcoma; Stomach Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Head and Neck Neoplasms; Melanoma; Sarcoma; Urinary Bladder Neoplasms; Sarcoma, Synovial; Liposarcoma, Myxoid; Physical Phenomena; Radiation
• Other Study ID Numbers: ADP-0044-001/RSS

Drug and device information, study documents

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