ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)

Purpose

This study will investigate the safety and tolerability of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and MAGE-A4 tumor antigen. Tumor indications include endometrial, esophageal, esophagogastric junction (EGJ), gastric, head and neck, melanoma, non-small cell lung (NSCLC), ovarian or urothelial cancer.

Conditions

  • Endometrial Cancer
  • Esophageal Cancer
  • Esophagogastric Junction (EGJ)
  • Gastric (Stomach) Cancer
  • Head and Neck Cancer
  • Melanoma
  • Ovarian Cancer
  • Non-small Cell Lung (NSCLC)
  • Urothelial Cancer

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age ≥18 and ≤ 75 years - Subject is positive for at least 1 HLA-A*02 inclusion allele - Histologically or cytogenetically confirmed diagnosis of urothelial cancer, esophageal, esophagogastric junction (EGJ) cancer, gastric cancer, non-small cell lung carcinoma (NSCLC), head and neck or ovarian cancer, endometrial cancer, melanoma - Measurable disease according to RECIST v1.1 prior to leukapheresis and lymphodepletion. - Tumor shows MAGE-A4 expression as confirmed by central laboratory - ECOG Performance Status of 0 or 1. - Left ventricular ejection fraction (LVEF) ≥50% or the institutional lower limit of normal range, whichever is lower Note: other protocol defined Inclusion/Exclusion criteria may apply - Subjects must have ≥ 90% room air oxygen saturation at rest at Screening (within 7 days of leukapheresis) and at Baseline.

Exclusion Criteria

  • Positive for any HLA-A*02 allele other than: one of the inclusion alleles - History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study - Active autoimmune or immune mediated disease - Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases - Other prior malignancy that is not considered by the Investigator to be in complete remission. Clinically significant cardiovascular disease - Uncontrolled intercurrent illness - Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus - Pregnant or breastfeeding Note: other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Autologous genetically modified ADP-A2M4CD8 cells
  • Genetic: Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks
    Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1 alone or in combination with either nivolumab 480 mg IV every four weeks or pembrolizumab 400mg IV every 6 weeks

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Donald P Lawrence
617-643-3614
dplawrence@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Adaptimmune

Study Contact

David Hong, MD
713-563-5844
dshong@madanderson.org

Detailed Description

Conditions: Endometrial Esophageal Cancer Esophagogastric Junction (EGJ) Gastric (stomach) Head and Neck Melanoma Non-small Cell Lung (NSCLC) Ovarian Cancer