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
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint 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
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.	3.5 years
Determining dose limiting toxicities (DLT) and optimally tolerated dose range	Evaluate DLTs and toxicity assessment using NCI CTCAE.	3.5 years
Evaluation of persistence of genetically modified T cells.	Evaluation of persistence of genetically modified T cells in the periphery.	3.5 years
Measurement of RCL in genetically modified T cells.	Evaluation of RCL in subject PBMCs using PCR-based assay.	3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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.	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.	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.	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.	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	15 years post last treatment (infusion)

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: Adaptimmune
• 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.

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): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

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: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Esophageal Diseases; Neoplasms, Connective Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms, Adipose Tissue; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sarcoma; Urinary Bladder Neoplasms; Melanoma; Esophageal Neoplasms; Liposarcoma; Liposarcoma, Myxoid; Sarcoma, Synovial
• 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