MAGE-A4ᶜ¹º³²T for Multi-Tumor

NCT03132922 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ADP-0044-001/RSS
• Study Type: interventional
• Target: 71
• Locations: 2 countries
• Sites: 11

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).

  3.5 years

• Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.

  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.

  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.

  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

  3.5 years

Other Outcomes (1)

• MAGE-A4c1032T cell trafficking in tumor lesion(s).

  3.5 years

Study Arms (2)

Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

EXPERIMENTAL

Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

Radiation Sub-Study: Autologous genetically modified MAGE-A4c1

EXPERIMENTAL

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

Interventions

Autologous genetically modified MAGE-A4ᶜ¹º³²T cells GENETIC

Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1

Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

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

Radiation Sub-Study: Autologous genetically modified MAGE-A4c1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Metastatic disease impinging on the spinal cord or threatening spinal cord compression.

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (11)

University of Miami

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Washington University

St Louis, Missouri, 63112, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Duke University Medical Center, Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Tennessee Oncology - Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G1X6, Canada

Location

Related Publications (2)

• 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.

  PMID: 36624315 DERIVED

• 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.

  PMID: 32002290 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Melanoma; Head and Neck Neoplasms; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms; Stomach Neoplasms; Sarcoma, Synovial; Liposarcoma, Myxoid; Neoplasm Metastasis; Adenocarcinoma; Sarcoma

Interventions

Radiation

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Liposarcoma; Neoplasms, Adipose Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• David Hong, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: April 28, 2017
• Study Start: May 15, 2017
• Primary Completion: December 27, 2022
• Study Completion (Estimated): September 1, 2032
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

CA (1); US (10)