Active, not recruiting
Phase 1
ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)
Condition(s) studied
Endometrial CancerEsophageal CancerEsophagogastric Junction (EGJ)Gastric (Stomach) CancerHead and Neck CancerMelanomaOvarian CancerNon-small Cell Lung (NSCLC)Urothelial Cancer
Investigational drug(s) / intervention(s)
Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks
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
Study summary
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.
Eligibility
* Key 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.
Key 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.
Primary outcome measure(s)
- To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab — 2.5 years
Determination of incidence of dose-limiting toxicities, adverse events and tolerable dose
- To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab — Up to 15 years
Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.
Trial sites (17)
| Facility | City | Region | Status |
| Name of Institution: Orlando Health Cancer Institute |
Orlando |
Florida |
|
| Massachusetts General Hospital |
Boston |
Massachusetts |
|
| Washington University - School of Medicine |
St Louis |
Missouri |
|
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
|
| Duke University Medical Center, Duke Cancer Institute |
Durham |
North Carolina |
|
| OU Health Stephenson Cancer Center |
Oklahoma City |
Oklahoma |
|
| Sarah Cannon Research Institute |
Nashville |
Tennessee |
|
| M.D. Anderson Cancer Center |
Houston |
Texas |
|
| Froedtert Hospital and the Medical College of Wisconsin |
Milwaukee |
Wisconsin |
|
| Princess Margaret Cancer Centre |
Toronto |
Ontario |
|
| Hospital Universitario 12 De Octubre |
Madrid |
Avenida de Cordoba S/n |
|
| Clinica Universitaria de Navarra |
Pío |
Pamplona |
|
| Hospital Clinico de Valencia |
Ibanez |
Valencia |
|
| Hospital Universitario Vall d'Hebron |
Barcelona |
Spain |
|
| Hospital Universitario Fundacion Jimenez Diaz |
Madrid |
Spain |
|
| Hospital Universitario HM Sanchinarro CIOCC |
Madrid |
Spain |
|
| Hospital Universitario Virgen del Rocio |
Seville |
Spain |
|