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

Primary Purpose

Ovarian Cancer

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Autologous genetically modified ADP-A2M4CD8 cells
Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab
Sponsored by
Adaptimmune
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: 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. Inclusion Criteria: 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 recurrent or metastatic disease, which may include investigational therapies unless discussed and agreed upon with the Sponsor or designee. 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. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Subject has left ventricular ejection fraction (LVEF) of ≥ 50% or the institutional lower limit of normal range, whichever is lower. Subject is fit for leukapheresis, and adequate venous access can be established for the cell collection. Subjects of childbearing potential must have a negative urine or serum pregnancy test AND must agree to use a highly effective method of contraception starting at the first dose of chemotherapy and continue for at least 12 months or for 4 months after the gene-modified cells are no longer detected in the blood, or 6 months after the last dose of nivolumab, whichever is longer. Subjects of childbearing potential must also agree to refrain from egg donation, storage, or banking during these same time periods. Subjects must have ≥ 90% room air oxygen saturation test at rest at Screening (within 7 days of leukapheresis) and at Baseline. Subject must have adequate organ function as indicated by the laboratory values in the table below. System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (without granulocyte colony stimulating factor [G-CSF] support) Platelets ≥ 100 × 109/L (without transfusion support within 5 days prior to leukapheresis and lymphodepletion) Hemoglobin (Hb) ≥ 90 g/L (without transfusion support within 5 days prior to leukapheresis and lymphodepletion) Coagulation Prothrombin time or international normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN), unless receiving therapeutic anticoagulation Partial thromboplastin time ≤ 1.5 × ULN, unless receiving therapeutic anticoagulation Renal Glomerular filtration rate (GFR) or creatinine clearance (CrCl) (estimated or calculated)1 ≥ 50 mL/min /1.73 m2 or ≥ 50 mL/min Hepatic Serum total bilirubin ≤ 1.5 × ULN (unless subject has documented Gilbert's Syndrome with direct bilirubin < 35% of total bilirubin) Exception: Subjects with liver metastasis ≤ 2.5 × ULN Alanine aminotransferase (ALT) / Aspartate aminotransferase (AST) ≤ 2.5 × ULN Exception: Subjects with liver metastasis ≤ 5.0 × ULN 1 Renal function (GFR or CrCl) will be estimated or measured according to standard practice at the treating institution. Renal function will be reassessed at Baseline using the same methodology. Note: Laboratory values that are slightly out of the laboratory test parameters, if assessed as not clinically significant by the site study Investigator, may be acceptable after discussion and review by the Sponsor Study Physician. This applies to screening laboratory assessments and baseline laboratory assessments. Exclusion Criteria: Positive for HLA-A*02:05 in either allele as determined by Adaptimmune-designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as HLA-A*02:05 in the peptide binding domains (P groups) will also be excluded. Other alleles may be exclusionary after adjudication with the Sponsor. 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: Toxicity from previous anti-cancer therapy that has not recovered to Grade ≤ 1 or baseline prior to enrollment (except for nonclinically significant toxicities, e.g., alopecia and vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled. Subject has a history of allergic reactions attributed to compounds of similar chemical or biological composition to fludarabine, cyclophosphamide, or other agents used in the study. Subject has an active autoimmune or immune-mediated disease that has not yet been resolved. Subjects with immune-mediated AEs secondary to treatment with immunotherapy that resolve to Grade ≤ 1 off steroids are permitted. Subjects with hypothyroidism, type I diabetes, adrenal insufficiency, or pituitary insufficiency that are stable on replacement therapy are eligible. Subjects with disorders such as asthma, vitiligo, psoriasis, or atopic dermatitis that are well controlled without requiring systemic immunosuppression are also eligible. Other stable immune conditions that do not require prednisone > 20 mg/day (or its equivalent for other corticosteroid agents) may be acceptable with the agreement of the Sponsor. Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical-related toxicities. Surgical-related toxicities that are not clinically significant per Investigator assessment may be acceptable after discussion and agreement with the Study Physician. Leptomeningeal disease, carcinomatous meningitis, or symptomatic central nervous system (CNS) metastases. Subjects with prior history of symptomatic CNS metastases must have received treatment (i.e., SRS, WBRT, or surgery) and be neurologically stable for at least 1 month, not requiring anti-seizure medications, or off steroids for at least 14 days prior to leukapheresis and lymphodepletion. Subjects who have asymptomatic CNS metastases without associated edema, shift, or requirement for steroids or anti-seizure medications are eligible. If such a subject receives SRS or WBRT, a minimum period of 2 weeks needs to lapse between the therapy and lymphodepletion. Prophylactic anti-seizure medication is allowed. Subject has any other prior malignancy that is not considered by the Investigator to be in complete remission. Resectable squamous or basal cell carcinoma of the skin is acceptable. Prior malignancies that have been surgically resected and show no evidence of disease are acceptable. Clinically significant cardiovascular disease including, but not limited to, any of the following: Electrocardiogram (ECG) showing clinically significant abnormality at Screening Uncontrolled clinically significant arrhythmias Known family history or congenital history of prolonged QT syndrome or history of torsade de pointes Uncontrolled hypertension despite optimal medical therapy Acute coronary syndrome (angina or myocardial infarction) in the last 6 months Clinically significant cardiac disease defined by congestive heart failure New York Heart Association Class 3 and 4 History of stroke, CNS bleeding, transient ischemic attack, or reversible ischemic neurologic deficit within last 6 months Uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active systemic infection, or localized infection which may become systemic due to leukapheresis procedure, e.g., catheter insertion will be excluded. Subjects with urinary tract infections will be included only following treatment with antibiotics.(For SARS-CoV 2 [COVID-19] infection, see Section 10.4.4.1) Clinically significant pulmonary disease with any 1 pulmonary function parameter < 60% predicted (forced expiratory volume first forced breath [FEV1], total lung capacity [TLC], or diffusing capacity of lungs for carbon monoxide [DLCO]; note: for patients with anemia, corrected DLCO could be used) assessed prior to leukapheresis and within 2 months of the start of lymphodepleting chemotherapy Requirement for oxygen support (due to cardiac or pulmonary disease) Interstitial lung disease (pneumonitis) or history of pneumonectomy or chronic obstructive pulmonary disease with ≥ 1 exacerbation within 1 year prior to the Screening Visit that required treatment with systemic corticosteroids or resulted in hospitalization Hospitalization for bowel obstruction in last 2 months Hematosis or significant organ bleeding in last 2 months Ascites or pleural effusion which requires repeated (2 within 4 weeks) paracentesis or thoracentesis within last 2 months Cardiac or pericardial tumor involvement (prior to lymphodepletion) Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human T cell leukemia virus (HTLV) as defined below. Re-screening for infectious disease markers is not required at baseline (prior to lymphodepletion) unless > 6 months has elapsed. Positive serology for HIV Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Subjects who are hepatitis B surface antigen negative but are hepatitis B core antibody-positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation. Prophylaxis should be initiated prior to lymphodepleting therapy and continued for 6 months. Active hepatitis C infection as demonstrated by hepatitis C ribonucleic acid (RNA) test. Subjects who are HCV antibody-positive will be screened for HCV RNA by any reverse transcription-polymerase chain reaction (RT PCR) or branched DNA (bDNA) assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value. Positive serology for HTLV 1 or 2 Subject is pregnant or breastfeeding. Subjects who have illicit drug or alcohol dependency within the past year. In the opinion of the Investigator, subject will be unlikely to fully comply with protocol requirements. Intolerance to nivolumab includes severe allergic reaction to nivolumab or any components (active or inactive) of nivolumab.

Sites / Locations

  • Honor Health
  • City of Hope
  • University of California
  • Orlando Health Cancer Institute
  • Tampa General Hospital Cancer Center
  • Augusta University
  • Karmanos Cancer Institute
  • Rutgers Cancer Institute of NJ
  • Vidant Medical Center
  • Cleveland Clinica Foundation
  • Ohio State University
  • University of Oklahoma Health Sciences CenterRecruiting
  • Avera Cancer InstituteRecruiting
  • University of Texas Southwestern Medical Center
  • Virginia Commonwealth University - Massey Cancer Center
  • Sewdish Cancer Institute
  • University Health Network (Princess Margaret Cancer Center)
  • Institut de Cancerologie des Hospices Civils de Lyon
  • Centre Leon-Berard
  • L'Institut du Cancer de Montpellier
  • Institut de Cancerologie de Strasbourg
  • Institut Gustave Roussy
  • Vall d'Hebron Unversity Hospital
  • Clinica Universidad de Navarra
  • Hospital Universitario Ramón y Cajal
  • Hospital Universitario 12 de Octubre
  • Centro Oncologico Clara Campal
  • Hospotal Clinico Universitario de Valencia
  • University College of London Hospital
  • The Royal Marsden NHS Foundation Trust
  • The Christie Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Autologous genetically modified ADP-A2M4CD8 cells

Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with nivolumab
Determination of incidence of adverse events and incidence, severity, and duration of AESIs
To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with nivolumab.
Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.
Durable Response (DR)
DR per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as a confirmed OR (CR or PR) lasting continuously for 6 months and starting any time within 12 months of T-cell infusion
Time to response (TTR)
TTR per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as the duration between the date of T-cell infusion and the initial date of the confirmed response.
Duration of Response (DOR)
DoR per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as the duration from the initial date of the confirmed response to the earliest date of PD or death due to any cause.
Progression Free Survival (PFS)
PFS per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as the interval between the date of T-cell infusion and the earliest date of disease progression or death due to any cause.
Overall Response (OR)
OR is defined as incidence of (confirmed) complete responses or partial responses as assessed by RECIST v1.1 by Investigator radiological assessment from T-cell infusion until documented disease progression
Overall Survival (OS)
OS, defined as the duration between the date of T-cell infusion and the date of death due to any cause.
Levels of serum CA125
Levels of serum CA125 (u/ml) for all patients
Levels of serum CA125
Changes of serum CA125 (u/ml) from baseline for all patients
To characterize the surrogates of treatment effect
Peak expansion (DNA copies/μg) (i.e., maximum persistence) by responder status and overall (all patients)
To characterize the surrogates of treatment effect
Time to peak expansion (in days since T-cell infusion) by responder status and overall (all patients)

Full Information

First Posted
October 26, 2022
Last Updated
August 25, 2023
Sponsor
Adaptimmune
Collaborators
GOG Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05601752
Brief Title
ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in HLA-A2+ Subjects With MAGE-A4 Positive Ovarian Cancer (SURPASS-3)
Official Title
A Phase 2, Open-Label, Randomized, Non-Comparative Clinical Trial of ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in Subjects With Recurrent Ovarian Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 26, 2023 (Actual)
Primary Completion Date
October 25, 2025 (Anticipated)
Study Completion Date
October 25, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adaptimmune
Collaborators
GOG Foundation

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Autologous genetically modified ADP-A2M4CD8 cells
Arm Type
Experimental
Arm Title
Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
Autologous genetically modified ADP-A2M4CD8 cells
Intervention Description
Infusion of autologous genetically modified ADP-A2M4CD8 cells on Day 1
Intervention Type
Combination Product
Intervention Name(s)
Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab
Intervention Description
Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1 followed by nivolumab 480 mg IV at Week 4 and then every four weeks
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
2.5 years
Secondary Outcome Measure Information:
Title
To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with nivolumab
Description
Determination of incidence of adverse events and incidence, severity, and duration of AESIs
Time Frame
2.5 years
Title
To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with nivolumab.
Description
Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.
Time Frame
15 years
Title
Durable Response (DR)
Description
DR per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as a confirmed OR (CR or PR) lasting continuously for 6 months and starting any time within 12 months of T-cell infusion
Time Frame
2.5 years
Title
Time to response (TTR)
Description
TTR per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as the duration between the date of T-cell infusion and the initial date of the confirmed response.
Time Frame
2.5 years
Title
Duration of Response (DOR)
Description
DoR per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as the duration from the initial date of the confirmed response to the earliest date of PD or death due to any cause.
Time Frame
2.5 years
Title
Progression Free Survival (PFS)
Description
PFS per RECIST v1.1 by IRAC and Investigator radiological assessment, defined as the interval between the date of T-cell infusion and the earliest date of disease progression or death due to any cause.
Time Frame
2.5 years
Title
Overall Response (OR)
Description
OR is defined as incidence of (confirmed) complete responses or partial responses as assessed by RECIST v1.1 by Investigator radiological assessment from T-cell infusion until documented disease progression
Time Frame
2.5 years
Title
Overall Survival (OS)
Description
OS, defined as the duration between the date of T-cell infusion and the date of death due to any cause.
Time Frame
15 years
Title
Levels of serum CA125
Description
Levels of serum CA125 (u/ml) for all patients
Time Frame
2.5 years
Title
Levels of serum CA125
Description
Changes of serum CA125 (u/ml) from baseline for all patients
Time Frame
2.5 years
Title
To characterize the surrogates of treatment effect
Description
Peak expansion (DNA copies/μg) (i.e., maximum persistence) by responder status and overall (all patients)
Time Frame
2.5 years
Title
To characterize the surrogates of treatment effect
Description
Time to peak expansion (in days since T-cell infusion) by responder status and overall (all patients)
Time Frame
2.5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Inclusion Criteria: 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 recurrent or metastatic disease, which may include investigational therapies unless discussed and agreed upon with the Sponsor or designee. 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. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Subject has left ventricular ejection fraction (LVEF) of ≥ 50% or the institutional lower limit of normal range, whichever is lower. Subject is fit for leukapheresis, and adequate venous access can be established for the cell collection. Subjects of childbearing potential must have a negative urine or serum pregnancy test AND must agree to use a highly effective method of contraception starting at the first dose of chemotherapy and continue for at least 12 months or for 4 months after the gene-modified cells are no longer detected in the blood, or 6 months after the last dose of nivolumab, whichever is longer. Subjects of childbearing potential must also agree to refrain from egg donation, storage, or banking during these same time periods. Subjects must have ≥ 90% room air oxygen saturation test at rest at Screening (within 7 days of leukapheresis) and at Baseline. Subject must have adequate organ function as indicated by the laboratory values in the table below. System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (without granulocyte colony stimulating factor [G-CSF] support) Platelets ≥ 100 × 109/L (without transfusion support within 5 days prior to leukapheresis and lymphodepletion) Hemoglobin (Hb) ≥ 90 g/L (without transfusion support within 5 days prior to leukapheresis and lymphodepletion) Coagulation Prothrombin time or international normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN), unless receiving therapeutic anticoagulation Partial thromboplastin time ≤ 1.5 × ULN, unless receiving therapeutic anticoagulation Renal Glomerular filtration rate (GFR) or creatinine clearance (CrCl) (estimated or calculated)1 ≥ 50 mL/min /1.73 m2 or ≥ 50 mL/min Hepatic Serum total bilirubin ≤ 1.5 × ULN (unless subject has documented Gilbert's Syndrome with direct bilirubin < 35% of total bilirubin) Exception: Subjects with liver metastasis ≤ 2.5 × ULN Alanine aminotransferase (ALT) / Aspartate aminotransferase (AST) ≤ 2.5 × ULN Exception: Subjects with liver metastasis ≤ 5.0 × ULN 1 Renal function (GFR or CrCl) will be estimated or measured according to standard practice at the treating institution. Renal function will be reassessed at Baseline using the same methodology. Note: Laboratory values that are slightly out of the laboratory test parameters, if assessed as not clinically significant by the site study Investigator, may be acceptable after discussion and review by the Sponsor Study Physician. This applies to screening laboratory assessments and baseline laboratory assessments. Exclusion Criteria: Positive for HLA-A*02:05 in either allele as determined by Adaptimmune-designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as HLA-A*02:05 in the peptide binding domains (P groups) will also be excluded. Other alleles may be exclusionary after adjudication with the Sponsor. 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: Toxicity from previous anti-cancer therapy that has not recovered to Grade ≤ 1 or baseline prior to enrollment (except for nonclinically significant toxicities, e.g., alopecia and vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled. Subject has a history of allergic reactions attributed to compounds of similar chemical or biological composition to fludarabine, cyclophosphamide, or other agents used in the study. Subject has an active autoimmune or immune-mediated disease that has not yet been resolved. Subjects with immune-mediated AEs secondary to treatment with immunotherapy that resolve to Grade ≤ 1 off steroids are permitted. Subjects with hypothyroidism, type I diabetes, adrenal insufficiency, or pituitary insufficiency that are stable on replacement therapy are eligible. Subjects with disorders such as asthma, vitiligo, psoriasis, or atopic dermatitis that are well controlled without requiring systemic immunosuppression are also eligible. Other stable immune conditions that do not require prednisone > 20 mg/day (or its equivalent for other corticosteroid agents) may be acceptable with the agreement of the Sponsor. Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical-related toxicities. Surgical-related toxicities that are not clinically significant per Investigator assessment may be acceptable after discussion and agreement with the Study Physician. Leptomeningeal disease, carcinomatous meningitis, or symptomatic central nervous system (CNS) metastases. Subjects with prior history of symptomatic CNS metastases must have received treatment (i.e., SRS, WBRT, or surgery) and be neurologically stable for at least 1 month, not requiring anti-seizure medications, or off steroids for at least 14 days prior to leukapheresis and lymphodepletion. Subjects who have asymptomatic CNS metastases without associated edema, shift, or requirement for steroids or anti-seizure medications are eligible. If such a subject receives SRS or WBRT, a minimum period of 2 weeks needs to lapse between the therapy and lymphodepletion. Prophylactic anti-seizure medication is allowed. Subject has any other prior malignancy that is not considered by the Investigator to be in complete remission. Resectable squamous or basal cell carcinoma of the skin is acceptable. Prior malignancies that have been surgically resected and show no evidence of disease are acceptable. Clinically significant cardiovascular disease including, but not limited to, any of the following: Electrocardiogram (ECG) showing clinically significant abnormality at Screening Uncontrolled clinically significant arrhythmias Known family history or congenital history of prolonged QT syndrome or history of torsade de pointes Uncontrolled hypertension despite optimal medical therapy Acute coronary syndrome (angina or myocardial infarction) in the last 6 months Clinically significant cardiac disease defined by congestive heart failure New York Heart Association Class 3 and 4 History of stroke, CNS bleeding, transient ischemic attack, or reversible ischemic neurologic deficit within last 6 months Uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active systemic infection, or localized infection which may become systemic due to leukapheresis procedure, e.g., catheter insertion will be excluded. Subjects with urinary tract infections will be included only following treatment with antibiotics.(For SARS-CoV 2 [COVID-19] infection, see Section 10.4.4.1) Clinically significant pulmonary disease with any 1 pulmonary function parameter < 60% predicted (forced expiratory volume first forced breath [FEV1], total lung capacity [TLC], or diffusing capacity of lungs for carbon monoxide [DLCO]; note: for patients with anemia, corrected DLCO could be used) assessed prior to leukapheresis and within 2 months of the start of lymphodepleting chemotherapy Requirement for oxygen support (due to cardiac or pulmonary disease) Interstitial lung disease (pneumonitis) or history of pneumonectomy or chronic obstructive pulmonary disease with ≥ 1 exacerbation within 1 year prior to the Screening Visit that required treatment with systemic corticosteroids or resulted in hospitalization Hospitalization for bowel obstruction in last 2 months Hematosis or significant organ bleeding in last 2 months Ascites or pleural effusion which requires repeated (2 within 4 weeks) paracentesis or thoracentesis within last 2 months Cardiac or pericardial tumor involvement (prior to lymphodepletion) Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human T cell leukemia virus (HTLV) as defined below. Re-screening for infectious disease markers is not required at baseline (prior to lymphodepletion) unless > 6 months has elapsed. Positive serology for HIV Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Subjects who are hepatitis B surface antigen negative but are hepatitis B core antibody-positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation. Prophylaxis should be initiated prior to lymphodepleting therapy and continued for 6 months. Active hepatitis C infection as demonstrated by hepatitis C ribonucleic acid (RNA) test. Subjects who are HCV antibody-positive will be screened for HCV RNA by any reverse transcription-polymerase chain reaction (RT PCR) or branched DNA (bDNA) assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value. Positive serology for HTLV 1 or 2 Subject is pregnant or breastfeeding. Subjects who have illicit drug or alcohol dependency within the past year. In the opinion of the Investigator, subject will be unlikely to fully comply with protocol requirements. Intolerance to nivolumab includes severe allergic reaction to nivolumab or any components (active or inactive) of nivolumab.
Facility Information:
Facility Name
Honor Health
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Justin Moser
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lorna Rodriguez
Facility Name
University of California
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramez Eskander
Facility Name
Orlando Health Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Not yet 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
Tampa General Hospital Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matt Anderson
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharad Ghamande
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Morris
Facility Name
Rutgers Cancer Institute of NJ
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anita Trupiano
Phone
732-454-9795
Email
ar2069@cinj.rutgers.edu
First Name & Middle Initial & Last Name & Degree
Kassie DiOrio
Facility Name
Vidant Medical Center
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darla Liles
Facility Name
Cleveland Clinica Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Rose
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David o'Malley
Facility Name
University of Oklahoma Health Sciences 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
Kathleen Moore
Phone
405-271-8707
Email
kathleen-moore@ouhsc.edu
Facility Name
Avera Cancer Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Starks
Phone
605-322-7535
Email
david.starks@avera.org
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Miller
Facility Name
Virginia Commonwealth University - Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leslie Randall
Facility Name
Sewdish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernanda Musa
Facility Name
University Health Network (Princess Margaret Cancer Center)
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neesha Dhani
Facility Name
Institut de Cancerologie des Hospices Civils de Lyon
City
Pierre-Bénite
State/Province
Lyon
ZIP/Postal Code
69310
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Centre Leon-Berard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Not yet recruiting
Facility Name
L'Institut du Cancer de Montpellier
City
Montpellier
ZIP/Postal Code
34090
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel Fabbro
Facility Name
Institut de Cancerologie de Strasbourg
City
Strasbourg
ZIP/Postal Code
67200
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Not yet recruiting
Facility Name
Vall d'Hebron Unversity Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Oaknin
Facility Name
Clinica Universidad de Navarra
City
Madrid
ZIP/Postal Code
28027
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Gonzalez-Martin
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alfonso C Salgado
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ainhoa Madariaga
Facility Name
Centro Oncologico Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arantzazu B Garcia
Facility Name
Hospotal Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andres MC Ruiperez
Facility Name
University College of London Hospital
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rowan Miller
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
W1G 0PL
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Furness
Facility Name
The Christie Hospital
City
Manchester
ZIP/Postal Code
M20 4GJ
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hasan Jurjees

12. IPD Sharing Statement

Learn more about this trial

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

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