ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in HLA-A2+ Subjects With MAGE-A4 Positive Ovarian Cancer (SURPASS-3)

NCT05601752 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ADP-0055-003/GOG-3084
• Study Type: interventional
• Target: 66
• Locations: 5 countries
• Sites: 23

Brief Summary

This is a phase 2, open-label, randomized, non-comparative clinical trial to evaluate the clinical outcome of ADP A2M4CD8 as monotherapy and in combination treatment with nivolumab in human leukocyte antigen (HLA) A2+ subjects with recurrent ovarian cancer positive for MAGE-A4.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the anti-tumor activity of genetically modified autologous T-cells (ADP-A2M4CD8) as monotherapy and in combination with nivolumab in HLA-A*02 positive subjects with MAGE-A4 positive recurrent ovarian cancer

  Overall Response (OR) is defined as incidence of (confirmed) complete responses or partial responses as assessed by RECIST v1.1 by IRAC from T-cell infusion until documented disease progression

  3.6 years

Secondary Outcomes (12)

• To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with nivolumab

  3.6 years

• To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with nivolumab.

  15 years

• Durable Response (DR)

  3.6 years

• Time to response (TTR)

  3.6 years

• Duration of Response (DOR)

  3.6 years

Study Arms (2)

Autologous genetically modified ADP-A2M4CD8 cells

EXPERIMENTAL

Genetic: Autologous genetically modified ADP-A2M4CD8 cells

Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab

EXPERIMENTAL

Combination Product: Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab

Interventions

Autologous genetically modified ADP-A2M4CD8 cells GENETIC

Infusion of autologous genetically modified ADP-A2M4CD8 cells on Day 1

Autologous genetically modified ADP-A2M4CD8 cells

Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab COMBINATION_PRODUCT

Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1 followed by nivolumab 480 mg IV at Week 4 and then every four weeks

Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will be assessed for eligibility prior to leukapheresis AND prior to lymphodepleting chemotherapy (unless otherwise noted) and must meet all specified criteria for study participation.
• Subject (or legally authorized representative) has voluntarily agreed to participate by giving written informed consent in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and applicable local regulations.
• Subject (or legally authorized representative) has agreed to abide by all protocol-required procedures including study related assessments and management by the treating institution for the duration of the study, including LTFU.
• Subject is ≥ 18 and ≤ 75 years of age at the time the Pre Screening informed consent form (ICF) is signed.
• Subject has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid recurrent ovarian carcinoma, including primary peritoneal and fallopian tube carcinoma.
• Subject has measurable disease according to RECIST v1.1 prior to lymphodepletion. Measurable disease is not required prior to leukapheresis.
• Subject has the following disease-specific prior therapy requirements:
• The initial therapy must have included at least 3 cycles of a prior platinum and taxane based chemotherapy regimen for primary disease, possibly including intraperitoneal therapy, consolidation, or extended therapy (maintenance/consolidation).
• Subjects may receive up to 4 prior regimens of combination or single agent systemic treatment for their disease, which may include investigational therapies unless discussed and agreed upon with the Sponsor or designee. Note: Neo-adjuvant/adjuvant treatment is considered as one line of treatment. Bridging therapy is permitted and is not considered as a line of treatment.
• Subjects who have received only 1 line of platinum based therapy must have progressed between 93 and 183 days of completing platinum based therapy as a part of front line treatment of ovarian cancer. Subjects who have progressed within 92 days of completing platinum based therapy in front line treatment are excluded.
• Subjects who have received 2 or more lines of platinum based therapy must have progressed during or within 183 days of completing the latest platinum based therapy for treatment of recurrent ovarian cancer. The number of days (platinum-free interval) should be calculated from the date of the last administered dose of platinum therapy to the date of documentation of progression.
• Subjects with a known BRCA mutation (germ line or somatic) must have received a poly adenosine diphosphate-ribose polymerase (PARP).
• Subjects must have received bevacizumab.
• Positive for HLA-A\*02:01, HLA-A\*02:02, HLA-A\*02:03, or HLA-A\*02:06 allele as determined by Adaptimmune-designated central laboratory testing. HLA-A\*02 alleles having the same protein sequence in the peptide binding domains (P group) will also be included. Other HLA-A\*02 alleles may be eligible after adjudication with the Sponsor.
• MAGE-A4 expression, defined as ≥ 30% of tumor cells that are ≥ 2+ by IHC, should be documented at the pre screening period based on either an archival specimen or a fresh biopsy. All samples must have been pathologically reviewed by an Adaptimmune-designated central laboratory confirming expression.

You may not qualify if:

• Subject has received or plans to receive the following therapy/treatment prior to to leukapheresis or lymphodepleting chemotherapy, unless stopped according to the washout requirements:
• Cytotoxic chemotherapy Required Washout Prior to Leukapheresis 3 weeks Required Washout Prior to Lymphodepletion: 3 weeks
• Small molecules/tyrosine kinase inhibitors (TKIs), such as dabrafenib, trametinib, vemurafenib, and cobimetinib Note: No washout period is required for compounds that do not cause bone marrow suppression/lymphopenia or for epidermal growth factor receptor and alkaline phosphatase/ ROS 1 inhibitors. Required Washout Prior to Leukapheresis 1 week Required Washout Prior to Lymphodepletion: 1 week
• Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors, and biologics) other than anti-PD(L)1 Required Washout Prior to Leukapheresis 2 weeks Required Washout Prior to Lymphodepletion: 2 weeks
• Anti-PD(L)1 Required Washout Prior to Leukapheresis 2 weeks Required Washout Prior to Lymphodepletion: 6 weeks
• Experimental anti-cancer vaccine Required Washout Prior to Leukapheresis: N/A Required Washout Prior to Lymphodepletion: Eight weeks in the absence of tumor response.
• The subject should be excluded if their disease is responding to an experimental vaccine given within 6 months.
• Gene therapy using an integrating vector Subjects who have received a gene therapy using any DNA-integrating vector other than a lentivirus (retrovirus, Adeno-associated Virus (AAV), etc.) are excluded from this study. Use of previous gene therapy using a lentiviral vector is permitted. If transduced T-cells represent \< 1% of PBMCs (\< 1500 copies of vectors/μg of PBMC DNA) at the time of screening. Eligibility testing must be done by Adaptimmune's designated Contract Research Organization (CRO). Required Washout Prior to Lymphodepletion: N/A
• Required Washout Prior to Leukapheresis: 2 weeks Required Washout Prior to Lymphodepletion 2 weeks
• Anti-MAGE-A4 therapy Note: Fresh screening biopsy post-anti-MAGE-A4 therapy must be obtained to confirm MAGE-A4 positivity by IHC. Required Washout Prior to Leukapheresis: 2 weeks Required Washout Prior to Lymphodepletion: 2 weeks
• Investigational treatment Required Washout Prior to Leukapheresis 2 weeks or 5 half-lives, whichever is shorter Required Washout Prior to Lymphodepletion: 2 weeks or 5 half-lives, whichever is shorter.
• Radiation to vital organs (e.g., liver, kidney) Required Washout Prior to Leukapheresis: N/A Required Washout Prior to Lymphodepletion: 4 weeks
• Radiation to the pelvis Required Washout Prior to Leukapheresis: 4 weeks Required Washout Prior to Lymphodepletion: 4 weeks
• Whole brain radiotherapy (WBRT) or brain stereotactic radiosurgery (SRS) Required Washout Prior to Leukapheresis N/A Required Washout Prior to Lymphodepletion: 2 weeks
• Radiotherapy to the target lesions Required Washout Prior to Leukapheresis: N/A Required Washout Prior to Lymphodepletion: 3 months prior to lymphodepleting chemotherapy or a target lesion with progression post radiotherapy (Note: There is no washout period for palliative radiation to non-target organs.)

Sponsors & Collaborators

• GOG Foundation: collaborator
• USWM CT, LLC: lead

Study Sites (23)

Honor Health

Scottsdale, Arizona, 85258, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Rutgers Cancer Institute of NJ

New Brunswick, New Jersey, 08901, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University Health Network (Princess Margaret Cancer Center)

Toronto, Ontario, M5G 2M9, Canada

Location

Institut de Cancerologie des Hospices Civils de Lyon

Pierre-Bénite, Lyon, 69310, France

Location

Centre Leon-Berard

Lyon, 69008, France

Location

Institut de Cancerologie de Strasbourg

Strasbourg, 67200, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Vall d'Hebron Unversity Hospital

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospotal Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

University College of London Hospital

London, NW1 2PG, United Kingdom

Location

The Christie Hospital

Manchester, M20 4GJ, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: November 1, 2022
• Study Start: June 26, 2023
• Primary Completion (Estimated): August 12, 2026
• Study Completion (Estimated): August 12, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

US (9); ES (7); CA (1); GB (2); FR (4)