MAGE-A4ᶜ¹º³²T for Multi-Tumor

• ClinicalTrials.gov Identifier: NCT03132922
• Recruitment Status: Active, not recruiting
• First Posted: April 28, 2017
• Last Update Posted: August 10, 2022
• Sponsor: Adaptimmune
• Information provided by (Responsible Party): Adaptimmune

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Urinary Bladder Cancer; Melanoma; Head and Neck Cancer; Ovarian Cancer; Non-Small Cell Lung Cancer; Esophageal Cancer; Gastric Cancer; Synovial Sarcoma; Myxoid Round Cell Liposarcoma; Gastroesophageal Junction	Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells; Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: May 15, 2017
• Estimated Primary Completion Date: September 2032
• Estimated Study Completion Date: September 2035

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of subjects with adverse events (AE), including serious adverse events (SAEs). [ Time Frame: 3.5 years ]
   Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.
2. Determining dose limiting toxicities (DLT) and optimally tolerated dose range [ Time Frame: 3.5 years ]
   Evaluate DLTs and toxicity assessment using NCI CTCAE.
3. Evaluation of persistence of genetically modified T cells. [ Time Frame: 3.5 years ]
   Evaluation of persistence of genetically modified T cells in the periphery.
4. Measurement of RCL in genetically modified T cells. [ Time Frame: 3.5 years ]
   Evaluation of RCL in subject PBMCs using PCR-based assay.

Secondary Outcome Measures :

1. Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR). [ Time Frame: 3.5 years ]
   Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
2. Interval between the date of first T cell infusion dose and first documented evidence of CR or PR. [ Time Frame: 3.5 years ]
   Evaluation of the efficacy of the treatment by assessment of time to first response.
3. Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause. [ Time Frame: 3.5 years ]
   Evaluation of the efficacy of the treatment by assessment of duration of response.
4. Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause. [ Time Frame: 3.5 years ]
   Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
5. Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause [ Time Frame: 3.5 years ]
   Evaluation of the efficacy of the treatment by assessment of progression-free survival.
6. Interval between the date of first T cell infusion and date of death due to any cause. [ Time Frame: 3.5 years ]
   Evaluation of the efficacy of the treatment by assessment of overall survival.
7. Number and % of subjects having any Long Term Follow Up Adverse Events (AEs) [ Time Frame: 15 years post last treatment (infusion) ]
   • 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

Other Outcome Measures:

1. MAGE-A4c1032T cell trafficking in tumor lesion(s). [ Time Frame: 3.5 years ]
   Evaluation of post-infusion T-cell trafficking in irradiated vs non-irradiation lesions

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

University of Miami

Miami, Florida, United States, 33136

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Washington University

Saint Louis, Missouri, United States, 63112

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

United States, North Carolina

Duke University Medical Center, Duke Cancer Institute

Durham, North Carolina, United States, 27710

United States, Ohio

Ohio State University Wexner Medical Center

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Tennessee

Tennessee Oncology - Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

M.D. Anderson Cancer Center

Houston, Texas, United States, 77030

Canada, Ontario

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G1X6

Sponsors and Collaborators

Adaptimmune

Investigators

• Principal Investigator: David Hong, MD; M.D. Anderson Cancer Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Adaptimmune
• ClinicalTrials.gov Identifier: NCT03132922
• Other Study ID Numbers: ADP-0044-001
• First Posted: April 28, 2017
• Last Update Posted: August 10, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Adaptimmune:

Cell Therapy; T Cell Therapy; SPEAR T Cell; MAGE-A4; Immuno-oncology; Metastatic; Urothelial Cancer; Previously Treated; T Cell Receptor; Squamous, adenosquamous, adenocarcinoma or large cell NSCLC; Squamous or adenocarcinoma esophageal cancer; Sarcoma; Melanoma; Bladder; Ovarian; Radiation therapy

Additional relevant MeSH terms:

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