Back to resultsADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)
Primary Purpose
Endometrial Cancer, Esophageal Cancer, Esophagogastric Junction (EGJ)
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks
Sponsored by
About this trial
This is an interventional treatment trial for Endometrial Cancer focused on measuring 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
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.
Sites / Locations
- Name of Institution: Orlando Health Cancer InstituteRecruiting
- Massachusetts General HospitalRecruiting
- Washington University - School of MedicineRecruiting
- Roswell Park Cancer Institute
- Memorial Sloan Kettering Cancer CenterRecruiting
- Duke University Medical Center, Duke Cancer InstituteRecruiting
- OU Health Stephenson Cancer CenterRecruiting
- Thomas Jefferson University Hospital
- Sarah Cannon Research InstituteRecruiting
- M.D. Anderson Cancer CenterRecruiting
- Froedtert Hospital and the Medical College of WisconsinRecruiting
- Cliniques Universitaires Saint-Luc
- University Hospital Antwerp
- Universitair Ziekenhuis Gent
- Princess Margaret Cancer CentreRecruiting
- Hospital Universitario 12 De OctubreRecruiting
- Clinica Universitaria de NavarraRecruiting
- Hospital Clinico de ValenciaRecruiting
- Hospital Universitario Vall d'HebronRecruiting
- Hospital Universitario Fundacion Jimenez DiazRecruiting
- Hospital Universitario HM Sanchinarro CIOCCRecruiting
- Hospital Universitario Virgen del RocioRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Autologous genetically modified ADP-A2M4CD8 cells
Arm Description
Outcomes
Primary Outcome Measures
To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
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
Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.
Secondary Outcome Measures
Anti-tumour activity: Overall Response Rate (ORR)
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
Anti-tumor activity: Best overall response (BOR)
BOR is per RECIST V1.1.
Time to response (TTR)
For patients who are observed to respond to ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab, the time taken to achieve a partial response or complete response (TTR) is assessed.
Duration of Response (DOR)
For patients who are observed to respond to ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab, the DOR is the date of first response (including confirmation) up until disease progression per RECIST v 1.1 or death
Duration of stable disease (DoSD)
For patients who are observed to have stable disease by RECIST v 1.1, the duration of period of stable disease until disease progression or death
Progression Free Survival (PFS)
PFS is assessed from date of infusion of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab up until the date of disease progression per RECIST v1.1 or death.
Overall Survival (OS)
OS is assessed from date of infusion of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab up until the date of patient death.
Full Information
NCT ID
NCT04044859
First Posted
July 3, 2019
Last Updated
August 22, 2023
Sponsor
Adaptimmune
Collaborators
ICON plc
1. Study Identification
Unique Protocol Identification Number
NCT04044859
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 20, 2019 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
April 30, 2037 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adaptimmune
Collaborators
ICON plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Autologous genetically modified ADP-A2M4CD8 cells
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks
Intervention Description
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
Primary Outcome Measure Information:
Title
To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
Description
Determination of incidence of dose-limiting toxicities, adverse events and tolerable dose
Time Frame
2.5 years
Title
To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
Description
Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.
Time Frame
Up to 15 years
Secondary Outcome Measure Information:
Title
Anti-tumour activity: Overall Response Rate (ORR)
Description
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
Time Frame
2.5 years
Title
Anti-tumor activity: Best overall response (BOR)
Description
BOR is per RECIST V1.1.
Time Frame
2.5 years
Title
Time to response (TTR)
Description
For patients who are observed to respond to ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab, the time taken to achieve a partial response or complete response (TTR) is assessed.
Time Frame
2.5 years
Title
Duration of Response (DOR)
Description
For patients who are observed to respond to ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab, the DOR is the date of first response (including confirmation) up until disease progression per RECIST v 1.1 or death
Time Frame
2.5 years
Title
Duration of stable disease (DoSD)
Description
For patients who are observed to have stable disease by RECIST v 1.1, the duration of period of stable disease until disease progression or death
Time Frame
2.5 years
Title
Progression Free Survival (PFS)
Description
PFS is assessed from date of infusion of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab up until the date of disease progression per RECIST v1.1 or death.
Time Frame
2.5 years
Title
Overall Survival (OS)
Description
OS is assessed from date of infusion of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab up until the date of patient death.
Time Frame
15 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Hong, MD
Phone
713-563-5844
Email
dshong@madanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Hong, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Name of Institution: Orlando Health Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sajeve S Thomas, MD
Phone
321-841-6780
Email
sajeve.thomas@orlandohealth.com
First Name & Middle Initial & Last Name & Degree
Sajeve S Thomas, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donald P Lawrence
Phone
617-643-3614
Email
dplawrence@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Donald Lawrence, MD
Facility Name
Washington University - School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Munsch
Phone
314-273-2726
Email
munschr@wustl.edu
First Name & Middle Initial & Last Name & Degree
Brian Van Tine, MD
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14040
Country
United States
Individual Site Status
Withdrawn
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Aggen, MD
Phone
646-608-2091
Email
cart@mskcc.org
First Name & Middle Initial & Last Name & Degree
David Aggen, MD
Facility Name
Duke University Medical Center, Duke Cancer Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex Guess
Phone
919-668-6406
Email
m.alex.guess@duke.edu
First Name & Middle Initial & Last Name & Degree
Jeffrey M Clarke, MD
Facility Name
OU Health Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silas Day
Phone
405-271-8001
Ext
48748
Email
Silas-Day@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
Adam Asch
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Withdrawn
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nurse Navigators
Phone
615-329-7274
First Name & Middle Initial & Last Name & Degree
Melissa L Johnson, MD
Facility Name
M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Hong, MD
Phone
713-563-1930
Email
dshong@mdanderson.org
First Name & Middle Initial & Last Name & Degree
David Hong, MD
Facility Name
Froedtert Hospital and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Neumann
Phone
414-805-8342
Email
jneumann@mcw.edu
First Name & Middle Initial & Last Name & Degree
John A Charlson, MD
Facility Name
Cliniques Universitaires Saint-Luc
City
Bruxelles
Country
Belgium
Individual Site Status
Withdrawn
Facility Name
University Hospital Antwerp
City
Edegem
Country
Belgium
Individual Site Status
Withdrawn
Facility Name
Universitair Ziekenhuis Gent
City
Gent
Country
Belgium
Individual Site Status
Withdrawn
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Genevieve Mendiola
Phone
416-634-7940
Email
genevieve.mendiola@uhn.ca
First Name & Middle Initial & Last Name & Degree
Marcus Butler, MD
Facility Name
Hospital Universitario 12 De Octubre
City
Madrid
State/Province
Avenida De Cordoba S/n
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Concha Hernandez
Phone
+34 91 390 89 22
Email
propuestasMI.hdoc@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Jon Zugazagoitia Fraile, MD
Facility Name
Clinica Universitaria de Navarra
City
Pio
State/Province
Pamplona
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariano Ponz-Sarvisé, MD PhD
Phone
+34 948 25 54 00
Email
mponz@unav.es
First Name & Middle Initial & Last Name & Degree
Mariano Ponz-Sarvisé, MD
Facility Name
Hospital Clinico de Valencia
City
Ibanez
State/Province
Valencia
ZIP/Postal Code
46010
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inma Blasco
Phone
961973527
Email
iblasco@incliva.es
First Name & Middle Initial & Last Name & Degree
Andres Cervantes Ruiperez, MD
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena G Cabanas, MD
Phone
(+34) 93 274 60 00
Ext
4846
Email
egarralda@vhio.net
First Name & Middle Initial & Last Name & Degree
Elena G Cabanas, MD
Facility Name
Hospital Universitario Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victor Moreno, MD
Phone
0034 91 550 48 00
Ext
2805
Email
fjd@startmadrid.com
First Name & Middle Initial & Last Name & Degree
Victor Moreno, MD
Facility Name
Hospital Universitario HM Sanchinarro CIOCC
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Esther Ordoñez
Phone
91 756 78 25
Email
ciocc@startmadrid.com
First Name & Middle Initial & Last Name & Degree
Emiliano Calvo Aller, MD
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Esperanza Muñoz
Phone
+34 600145696
Email
espe.m.garcia@gmail.com
First Name & Middle Initial & Last Name & Degree
Reyes Bernabe Caro, MD
12. IPD Sharing Statement
Learn more about this trial
ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)
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