MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC

NCT02592577 | Completed Phase 1 FDA Drug

• 1 other identifier: ADP 0022-003
• Study Type: interventional
• Target: 28
• Locations: 4 countries
• Sites: 19

Brief Summary

This first time in human study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A\*02:01 and/or HLA-A\*02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .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 receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the 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 lung cancer. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose. Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years. Subjects who have a confirmed response or clinical benefit ≥4 weeks after the first T-cell infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the Interventional Phase of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.

Conditions

Carcinoma; Non-Small Cell Lung Cancer

Keywords

Previously Treated; Cell Therapy; T Cell Therapy; MAGE-A10; Immuno-oncology; T Cell Receptor; Metastatic

Outcome Measures

Primary Outcomes (1)

• Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE)

  Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; cardiac and pulmonary assessments, including ECG and troponin.

  24 months

Secondary Outcomes (8)

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

  24 months

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

  24 months

• Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause

  24 months

• Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause

  24 months

• Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause

  24 months

Study Arms (1)

Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

EXPERIMENTAL

Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

Interventions

Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T BIOLOGICAL

Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

Eligibility Criteria

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

You may qualify if:

• Subject has histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease
• Subject has received at least one line of prior therapy
• Subjects with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (progressive disease or unacceptable toxicity) at least one prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively. Subject may have received PD-1 or PDL-1 inhibitors and or chemotherapy. There is no limit on lines of prior anti-cancer therapy (a washout period applies for recent anti-cancer treatments).
• Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
• Subject is HLA-A\*02:01 or HLA-A\*02:06 positive.
• Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by a designated central laboratory confirming MAGE-A10 expression.
• Subject has an ECOG Performance Status 0-1 and anticipated life expectancy \>6 months prior to apheresis and \>3 months prior to lymphodepletion.
• Subject is ≥18 to ≤75 years of age
• Adequate organ function

You may not qualify if:

• Subject is HLA-A\*02:05, HLA-B\*15:01 and/or HLA-B\*46:01 positive.
• History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
• Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.
• Active malignancy besides NSCLC within 3 years prior to screening.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection;
• Clinically significant cardiac disease
• Inadequate pulmonary function
• Interstitial lung disease

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (19)

City of Hope

Duarte, California, 91010, United States

Location

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46033, United States

Location

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, 21157, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University, School of Medicine

St Louis, Missouri, 63110, 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

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G1X6, Canada

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario 12 Octubre Avda. de Córdoba s/n

Madrid, Madrid, 28041, Spain

Location

University College Hospital Macmillan Cancer Centre

London, WC1E 6AG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Blumenschein GR, Devarakonda S, Johnson M, Moreno V, Gainor J, Edelman MJ, Heymach JV, Govindan R, Bachier C, Doger de Speville B, Frigault MJ, Olszanski AJ, Lam VK, Hyland N, Navenot JM, Fayngerts S, Wolchinsky Z, Broad R, Batrakou D, Pentony MM, Sanderson JP, Gerry A, Marks D, Bai J, Holdich T, Norry E, Fracasso PM. Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer. J Immunother Cancer. 2022 Jan;10(1):e003581. doi: 10.1136/jitc-2021-003581.

  PMID: 35086946 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ben Creelan, MD, MS

  H. Lee Moffitt Cancer Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 30, 2015
• Study Start: November 1, 2015
• Primary Completion: March 11, 2020
• Study Completion: March 17, 2021
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

ES (2); US (14); GB (2); CA (1)