MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC

A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma; Non-Small Cell Lung Cancer
• Intervention / Treatment: Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X6
      • Princess Margaret Cancer Centre
• Spain
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 Octubre Avda. de Córdoba s/n
• United Kingdom
  • London, United Kingdom, WC1E 6AG
    • University College Hospital Macmillan Cancer Centre
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46033
      • Indiana University Simon Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21157
      • University of Maryland, Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, School of Medicine
  • 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
      • The University of Texas Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Subject has histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease
2. Subject has received at least one line of prior therapy
3. 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).
4. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
5. Subject is HLA-A*02:01 or HLA-A*02:06 positive.
6. 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.
7. Subject has an ECOG Performance Status 0-1 and anticipated life expectancy >6 months prior to apheresis and >3 months prior to lymphodepletion.
8. Subject is ≥18 to ≤75 years of age
9. Adequate organ function

Key Exclusion Criteria:

1. Subject is HLA-A*02:05, HLA-B*15:01 and/or HLA-B*46:01 positive.
2. 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.
3. 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.
4. Active malignancy besides NSCLC within 3 years prior to screening.

5. Uncontrolled intercurrent illness including, but not limited to:

   • Ongoing or active infection;
   • Clinically significant cardiac disease
   • Inadequate pulmonary function
   • Interstitial lung disease

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 T cells, MAGEA10ᶜ⁷⁹⁶T	Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR)	Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1	24 months
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	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	Evaluation of the efficacy of the treatment by assessment of duration of response	24 months
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	24 months
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	24 months
Interval between the date of first T cell infusion and date of disease progression or death due to any cause	Evaluation of the efficacy of the treatment by assessment of overall survival	24 months
Best Overall Response (BOR)	Best Overall Response (BOR), defined as the best response recorded from the date of T cell infusion until disease progression	24 months
To evaluate potential gene therapy-related delayed adverse events for 15 years post infusion.	Presence of any of the following LTFU AEs: New malignancies; New incidence or exacerbation of a pre-existing neurologic disorder; New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder; New incidence of a hematologic disorder; Opportunistic and/or serious infections; Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy Persistence of MAGE-A10c796T and replication-competent lentivirus (RCL) over time.	15 years

Collaborators and Investigators

• Sponsor: Adaptimmune
• Investigators: Study Chair: Ben Creelan, MD, MS, H. Lee Moffitt Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): March 11, 2020
• Study Completion (Actual): March 17, 2021

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 29, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Cell Therapy; Metastatic; Immuno-oncology; T Cell Therapy; T Cell Receptor; Previously Treated; MAGE-A10
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ADP 0022-003

Drug and device information, study documents

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