Clinical trial NCT04044859: ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)
Official title: A Phase 1 Dose Escalation Study To Assess Safety And Efficacy Of ADP-A2M4CD8 As Monotherapy Or In Combination With Either Nivolumab Or Pembrolizumab In HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Keywords: Cell Therapy
T Cell Therapy
SPEAR T Cell
MAGE-A4
Immuno-oncology
Metastatic
Urothelial
Head and Neck
Gastric (stomach)
Esophagogastric Junction (EGJ)
Non-small Cell Lung (NSCLC)
Esophageal Cancer
Ovarian Cancer
Endometrial Cancer
Melanoma
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
First posted: 2019-08-05
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Conditions:

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

Eligibility criteria: * 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 outcomes:
measure: To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
timeFrame: 2.5 years
measure: To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
timeFrame: Up to 15 years
Secondary outcomes:
measure: Anti-tumour activity: Overall Response Rate (ORR)
timeFrame: 2.5 years
measure: Anti-tumor activity: Best overall response (BOR)
timeFrame: 2.5 years
measure: Time to response (TTR)
timeFrame: 2.5 years
measure: Duration of Response (DOR)
timeFrame: 2.5 years
measure: Duration of stable disease (DoSD)
timeFrame: 2.5 years
measure: Progression Free Survival (PFS)
timeFrame: 2.5 years
measure: Overall Survival (OS)
timeFrame: 15 years
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Name of Institution: Orlando Health Cancer Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University - School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Duke Cancer Institute
state: North Carolina
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
state: Avenida de Cordoba s/n
city: Pio
country: Spain
facility: Clinica Universitaria de Navarra
state: Pamplona
city: Ibanez
country: Spain
facility: Hospital Clinico de Valencia
state: Valencia
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro CIOCC
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Hong, MD
role: PRINCIPAL_INVESTIGATOR
References: