Clinical trial NCT05617755: AB-1015, an Integrated Circuit T (ICT) Cell Therapy in Patients with Platinum Resistant Epithelial Ovarian Cancer
Official title: An Open-label Phase 1 Study to Evaluate the Safety and Efficacy of AB-1015 in Patients with Resistant/Refractory Epithelial Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Ovarian Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Diseases
Genital Neoplasm, Female
Abdominal Neoplasm
Recurrence
Keywords: ovarian cancer
fallopian tube cancer
primary peritoneal cancer
platinum resistant
Lead sponsor: Arsenal Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-15
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events and dose limiting toxicities (DLTs)
timeFrame: Up to 2 years post treatment
measure: Maximal tolerated dose of AB-1015
timeFrame: Up to 21 days
Secondary outcomes:
measure: Number of AB-1015 cells
timeFrame: Up to 1 year post treatment
measure: Evidence of anti-tumor activity
timeFrame: Up to 2 years post treatment
measure: Co-expression of ALPG and MSLN targets on tumor cells
timeFrame: Up to 2 years post treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: U of Colorado Cancer Center - Anschutz Medical Campus
state: Colorado
city: Iowa City
country: United States
facility: U of Iowa Health Care
state: Iowa
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: U of Washington - Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Arsenal Biosciences
name: Arsenal Biosciences
role: STUDY_DIRECTOR
References: