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

Ovarian Cancer Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04044859
• Other study ID #: ADP-0055-001
• Status: Recruiting
• Phase: Phase 1
• Start date: August 20, 2019
• Est. completion date: April 30, 2037

Study information

• Verified date: February 2024
• Source: Adaptimmune
• Contact: David Hong, MD
• Phone: 713-563-5844
• Email: dshong[@]madanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Conditions:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: April 30, 2037
• Est. primary completion date: December 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

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.

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms
• Esophageal Cancer
• Esophageal Neoplasms
• Gastric (Stomach) Cancer
• Head and Neck Cancer
• Melanoma
• Ovarian Cancer
• Ovarian Neoplasms
• Stomach Neoplasms
• Urothelial Cancer

Intervention

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

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	University Hospital Antwerp	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Clinico de Valencia	Ibanez	Valencia
Spain	Hospital Universitario 12 De Octubre	Madrid	Avenida De Cordoba S/n
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario HM Sanchinarro CIOCC	Madrid
Spain	Clinica Universitaria de Navarra	Pio	Pamplona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Duke University Medical Center, Duke Cancer Institute	Durham	North Carolina
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Name of Institution: Orlando Health Cancer Institute	Orlando	Florida
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Washington University - School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Adaptimmune	ICON plc

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2.5 years
Primary	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.	Up to 15 years
Secondary	Anti-tumour activity: Overall Response Rate (ORR)	ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1	2.5 years
Secondary	Anti-tumor activity: Best overall response (BOR)	BOR is per RECIST V1.1.	2.5 years
Secondary	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.	2.5 years
Secondary	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	2.5 years
Secondary	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	2.5 years
Secondary	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.	2.5 years
Secondary	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.	15 years