AB-1015, an Integrated Circuit T (ICT) Cell Therapy in Patients With Platinum Resistant Epithelial Ovarian Cancer

Study Overview
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Brief Summary
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This is a multi-center, open-label phase 1 dose escalation trial that uses a modified 3+3 design to identify a recommended phase 2 dose (RP2D) of AB-1015 cell product. Backfill cohorts will enroll additional subjects at doses deemed to be safe for a total enrollment of up to 12 subjects per each backfill cohort on the protocol.

Detailed Description
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This study is intended for the patients who have been diagnosed with Epithelial Ovarian Cancer that either came back or did not improve after platinum treatments (platinum resistant). The purpose of this study is to test the safety of using a new treatment called Integrated Circuit T (ICT) cells (AB-1015 cells) in patients with ovarian cancer. This treatment has not been approved by the Food and Drug Administration. The goal of this study is to calculate the maximum tolerated dose of the AB-1015 cells. T cells are part of the immune system that protect the body from infection and may help fight cancer. The T cells given in this study will come from the patient and will have a genetic circuit/logic gate put in them that makes them able to recognize alkaline phosphatase, germ line/placental (ALPG/P) and mesothelin (MSLN), 2 proteins on the surface of tumor cells. These logic-gated T cells may help the body's immune system identify and kill cancer cells while sparing normal healthy tissues from toxicity. The AB-1015 cells are given intravenously, after completing 3 rounds of conditioning chemotherapy administered over 3 consecutive days. Conditioning chemotherapy prepares the body to receive the AB-1015 cells. If they continue to meet the eligibility criteria, AB-1015 cells will be given to them 2 days after the last conditioning chemotherapy round. A single infusion of the AB-1015 cells will be given to the subject intravenously. After completion of study treatment, patients are followed with serial measurements of safety, tolerability and response. This is a research study to obtain new information that may help people in the future.

Official Title
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An Open-label Phase 1 Study to Evaluate the Safety and Efficacy of AB-1015 in Patients With Resistant/Refractory Epithelial Ovarian Cancer

Conditions
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Carcinoma, Ovarian Epithelial, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms, Neoplasms, Glandular and Epithelial, Ovarian Diseases, Genital Neoplasm, Female, Abdominal Neoplasm, Recurrence

Intervention / Treatment
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* Biological: AB-1015


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent, advanced, platinum resistant ovarian, fallopian tube, and primary peritoneal cancer and must have a histological diagnosis of a high-grade serous histology. a) Platinum resistant disease is defined as progression of disease within six months of platinum regimen. Doubling of cancer antigen 125 (CA-125) level on 2 successive measurements may be considered as meeting the definition of disease progression b) Have received at least 2 lines of prior therapy including a platinum-based regimen if eligible and a poly-ADP ribose polymerase (PARP) inhibitor if BRCA1/2 mutated. No more than 3 lines of prior therapy for the treatment of platinum resistant disease is permitted. Adequate organ function as per protocol definitions. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1. Evaluable disease (dose escalation cohorts) or measurable disease (backfill cohorts) at time of enrollment as per protocol definitions. Negative pregnancy test for women of childbearing potential. Women of non-childbearing potential are those who have been surgically sterilized, have medically confirmed ovarian failure, or have not had menses within the past 12 months. Exclusion Criteria: Cytotoxic chemotherapy within 14 days of time of cell collection. Cytotoxic chemotherapy within 14 days of starting of conditioning chemotherapy. New York Heart Association functional class II-IV cardiovascular disability Clinically significant pericardial effusion Pleural or peritoneal effusion that requires drainage for symptom management within 28 days of screening. Active autoimmune disease requiring immunosuppressive therapy or uncontrolled with treatment. Untreated brain metastasis. Subjects unwilling to participate in an extended safety monitoring period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AB-1015<br>Patients receive fludarabine and cyclophosphamide intravenously on days -5 to -3. Patients receive a single dose of AB-1015 intravenously on day 0. | Biological: AB-1015<br>* autologous T cell therapy<br>* Other names: Integrated Circuit T (ICT) cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and dose limiting toxicities (DLTs) | Toxicity grading will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 5.0 and monitoring of adverse events. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events will be graded according to the criteria outlined in the protocol. | Up to 2 years post treatment | 
| Maximal tolerated dose of AB-1015 | Will be determined by a 3x3 dose escalation study | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of AB-1015 cells | Number of AB-1015 cells present in patients treatment with AB-1015 | Up to 1 year post treatment | 
| Evidence of anti-tumor activity | Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Up to 2 years post treatment | 
| Co-expression of ALPG and MSLN targets on tumor cells | Assessment by immunohistochemistry (or similar method) | Up to 2 years post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, fallopian tube cancer, primary peritoneal cancer, platinum resistant