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

• ClinicalTrials.gov Identifier: NCT04044859
• Recruitment Status: Recruiting
• First Posted: August 5, 2019
• Last Update Posted: February 16, 2024
• Sponsor: Adaptimmune
• Collaborator: ICON plc
• Information provided by (Responsible Party): Adaptimmune

Tracking Information

• First Submitted Date: July 3, 2019
• First Posted Date: August 5, 2019
• Last Update Posted Date: February 16, 2024
• Actual Study Start Date: August 20, 2019
• Estimated Primary Completion Date: December 23, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2023)

• To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab [ Time Frame: 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 [ Time Frame: Up to 15 years ]
  Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.

Original Primary Outcome Measures (submitted: August 1, 2019)

• Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: 2.5 years ]
  Determine if treatment with ADP-A2M4CD8 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs)
• Evaluate safety of ADP-A2M4CD8 through measurement of Replication -competent Retrovirus in genetically engineered T-cells [ Time Frame: 15 years ]
  Evaluation of RCL using PCR -based assay in peripheral blood.

Current Secondary Outcome Measures (submitted: February 2, 2023)

• Anti-tumour activity: Overall Response Rate (ORR) [ Time Frame: 2.5 years ]
  ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
• Anti-tumor activity: Best overall response (BOR) [ Time Frame: 2.5 years ]
  BOR is per RECIST V1.1.
• Time to response (TTR) [ Time Frame: 2.5 years ]
  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) [ Time Frame: 2.5 years ]
  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) [ Time Frame: 2.5 years ]
  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) [ Time Frame: 2.5 years ]
  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) [ Time Frame: 15 years ]
  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.

Original Secondary Outcome Measures (submitted: August 1, 2019)

• Anti-tumour activity: Overall Response Rate (ORR) [ Time Frame: 2.5 years ]
  ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
• Anti-tumor activity: Best overall response (BOR) [ Time Frame: 2.5 years ]
  BOR is per RECIST V1.1.
• Time to response (TTR) [ Time Frame: 2.5 years ]
  For patients who are observed to respond to ADP-A2M4CD8, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed
• Duration of Response (DOR) [ Time Frame: 2.5 years ]
  For patients who are observed to respond to ADP-A2M4CD8, the DOR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death.
• Duration of stable disease (DoSD) [ Time Frame: 2.5 years ]
  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) [ Time Frame: 2.5 years ]
  PFS is assessed from date of infusion of ADP-A2M4CD8 up until the date of disease progression per RECIST v1.1 or death.
• Overall Survival (OS) [ Time Frame: 15 years ]
  OS is assessed from date of infusion of ADP-A2M4CD8 up until the date of patient death.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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

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

Condition

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

Study Arms

Experimental: Autologous genetically modified ADP-A2M4CD8 cells

Intervention: Genetic: Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 2, 2023): 120
• Original Estimated Enrollment (submitted: August 1, 2019): 30
• Estimated Study Completion Date: April 30, 2037
• Estimated Primary Completion Date: December 23, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Belgium, Canada, Spain, United States

Administrative Information

• NCT Number: NCT04044859
• Other Study ID Numbers: ADP-0055-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Adaptimmune
• Original Responsible Party: Same as current
• Current Study Sponsor: Adaptimmune
• Original Study Sponsor: Same as current
• Collaborators: ICON plc

Investigators

• Principal Investigator: David Hong, MD; M.D. Anderson Cancer Center

• PRS Account: Adaptimmune
• Verification Date: February 2024