MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers

Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors

This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose.

The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer.

Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.

Study Overview

• Status: Completed
• Conditions: Melanoma; Head and Neck Cancer; Urothelial Carcinoma; Bladder Urothelial Carcinoma
• Intervention / Treatment: Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X6
      • Princess Margaret Cancer Centre
• Spain
  • Madrid, Spain, 28040
    • Start Madrid-FJD, Fundación Jimѐnez Díaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 Octubre Avda. de Córdoba
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University - School of Medicine
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park 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
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt - Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD 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 following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
3. Subject is HLA-A*02:01 and/or HLA-A*02:06 positive.
4. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
5. Subject meets disease-specific requirements per protocol
6. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
7. Subject's tumor shows positive MAGE-A10 expression
8. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
9. Subject has a left ventricular ejection fraction ≥50%.
10. Subject is fit for leukapheresis and has adequate venous access for the cell collection.
11. Female subject of childbearing potential (FCBP) must have a negative urine or serum pregnancy test or male subject must be surgically sterile or agree to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential starting at the first dose of chemotherapy and for 4 months thereafter.
12. Subject must have adequate organ function per protocol

Exclusion Criteria:

1. Subject is HLA-A*02:05 in either allele, HLA-B*15:01 and/or HLA-B*46:01 positive. Subject has any A*02 null allele (designated with an "N", e.g. A*02:32N) as the sole HLA-A*02 allele.
2. Subject has received or plans to receive excluded therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy per protocol
3. Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 prior to enrollment
4. Subject has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
5. Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
6. Subject has an electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with bundle branch block [BBB]) over 3 consecutive ECGs. Either Fridericia's or Bazett's formula may be used to correct the QT interval.
7. Subject has symptomatic CNS metastases.
8. Subject has a history of chronic or recurrent severe autoimmune or immune mediated disease
9. Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening.
10. Subject has uncontrolled intercurrent illness
11. Subject has active infection with HIV, HBV, HCV or HTLV
12. Subject is pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells	Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells; Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Number of subjects with adverse events (AE), including serious adverse events (SAE).	Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin.	3 years
Evaluation of the persistence of genetically modified T cells	Evaluation of the persistence of the infused T cells in the periphery.	3 years
Measurement of RCL in genetically modified T cells.	Evaluation of RCL in Subject PBMCs using PCR-based assay.	3 years
Assessment of dose limiting toxicities to determine optimally tolerated dose range	Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0	3 years
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 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 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 years
Interval between the date of first documented evidence of 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 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 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 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Hong DS, Butler MO, Pachynski RK, Sullivan R, Kebriaei P, Boross-Harmer S, Ghobadi A, Frigault MJ, Dumbrava EE, Sauer A, Brophy F, Navenot JM, Fayngerts S, Wolchinsky Z, Broad R, Batrakou DG, Wang R, Solis LM, Duose DY, Sanderson JP, Gerry AB, Marks D, Bai J, Norry E, Fracasso PM. Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. Front Oncol. 2022 Mar 18;12:818679. doi: 10.3389/fonc.2022.818679. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): December 18, 2019
• Study Completion (Actual): June 4, 2020

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: December 7, 2016
• First Posted (Estimated): December 12, 2016

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Cancer; Advanced; Metastatic; Melanoma; Bladder; Urothelial Cancer; Inoperable; Immuno-oncology; T Cell Therapy; T Cell Receptor; SPEAR T Cell; Head and neck; Previously Treated; MAGE-A10
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasms; Neoplasm Metastasis; Head and Neck Neoplasms; Melanoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: ADP-0022-004

Drug and device information, study documents

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