A Phase I 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 Identifier:
ADP-0055-001
CT.gov Identifier:
NCT04044859
EudraCT Identifier:
2019-001965-34
EU Trial (CTIS) Number:
2024-512864-71-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To evaluate safety, tolerability and antitumor activity ADP-A2M4CD8 in patients with HLA-A*02 with MAGE-A4+ locally advanced inoperable or metastatic multiple solid cancers.

To characterize safety, tolerability, and antitumor activity across multiple tumor types.

Safety, efficacy, pharmacokinetics, pharmacodynamics, and tumor biopsy characterization are evaluated.

To evaluate ADP-A2M4CD8 in combination with a checkpoint inhibitor in the second line setting in urothelial cancers

To evaluate ADP--A2M4CD8 in combination with first-line standard of care (pembrolizumab) in head & neck cancer

To report updated clinical outcomes in patients with urothelial cancer (UC).

Autologous T-cells are obtained by leukapheresis, transduced with a self-inactivating lentiviral vector expressing the MAGE-A4-specific T-cell receptor and the CD8α co-receptor, and infused back to the patients as ADP-A2M4CD8 following lymphodepleting chemotherapy.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
  • Non-Small Cell Lung Cancer
  • Ovarian
  • Melanoma
  • Renal
  • Gastric
  • Head & Neck
  • Solid Tumor
  • Soft Tissue Sarcoma
  • Endometrial
  • Esophageal
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18 - 75 Years
    Study Drug
  • Drug: Lymphodepletion: Flu (30 mg/m2/day) × 4 days; Cy (1800 mg/m2/day) × 2 days
    • Read More
  • Drug: This is a three-cohort dose escalation study. patients will be shorter and the starting dose in the first cohort will be 0.8 to 1.2 billion SPEAR T-cells, instead of 100 million SPEAR T-cells. Each dose cohort will enroll 3 patients and can be expanded to 6 patients if a dose limiting toxicity occurs. The dose ranges for the other two cohorts are: 1.2 to 3 billion and 3 to 6 billion SPEAR T-cells. After dose escalation is complete, there is an expansion phase with doses up to 10 billion cells.
  • Drug: Genetic: Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks
  • Drug: Prior to ADP-A2M4CD8 infusion, patients will receive lymphodepletion consisting of fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (600 mg/m2/day x 3 days). During dose escalation, patients will be treated in one of three ADP-A2M4CD8 dose groups. The initial dose of ADP-A2M4CD8 will be 0.8 × 10^9 - 1.2 × 10^9 to be escalated to 1.2 × 10^9 - 3 × 10^9 and then to 3.0 × 10^9 - 6.0 × 10^9 transduced cells in a modified 3 + 3 dose escalation scheme. Patients will be monitored for doselimiting toxicities (DLTs). Once the tolerability and safety of the lymphodepletion regimen and cell dose has been demonstrated, the dose range will increase to a maximum of 10 × 10^9 transduced cells in the expansion phase.
  • Drug: Cohorts 2 and 3 were merged and 3 patients will be treated in this new group with up to 5 billion SPEAR T-cells, before moving into the expansion phase
  • Drug: SITC 2020:
  • Drug: pts also received nivolumab 480 mg every 4 weeks until unacceptable toxicity/disease progression
  • Drug: ASCO GU 2024:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Key Inclusion criteria
    • Age >or = 18 and
    • 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.
    • 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 > or = 90% room air oxygen saturation at rest at Screening (within 7 days of leukapheresis) and at Baseline.
    • Key eligibility criteria include >30% of tumor cells expressing MAGE-A4 (≥2+ by immunohistochemistry); positivity for HLA-A*02:01, 02:02, 02:03, or 02:06 alleles; measurable disease per RECIST v1.1 prior to lymphodepletion; and ECOG performance status of 0 or 1.
    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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Bladder
    Non-Small Cell Lung Cancer
    Ovarian
    Melanoma
    Renal
    Gastric
    Head & Neck
    Solid Tumor
    Soft Tissue Sarcoma
    Endometrial
    Esophageal
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Emiliano Calvo
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Bladder
    Non-Small Cell Lung Cancer
    Ovarian
    Melanoma
    Renal
    Gastric
    Head & Neck
    Solid Tumor
    Soft Tissue Sarcoma
    Endometrial
    Esophageal