CAR-T cell therapy for ovarian cancer enters next phase of testing
Clinical trial dosing 4th patient group to determine maximum tolerated dose
A Phase 1 clinical trial evaluating escalating doses of Anixa Biosciences’ experimental CAR T-cell therapy for recurrent ovarian cancer has begun dosing participants in its fourth dose group.
This first-in-human Phase 1 trial (NCT05316129), conducted in collaboration with Moffitt Cancer Center in Florida, is assessing the safety, tolerability, and preliminary efficacy of the therapy in women with ovarian cancer that has progressed after at least one platinum-based chemotherapy and at least two prior chemotherapy regimens.
The fourth group of patients is receiving a dose of 3 million CAR T-cells per kilogram (kg) of body weight, following favorable safety data from the third group of women who were treated with 1 million cells/kg.
“With no dose-limiting safety issues observed in the third cohort, we have advanced to a higher dose level that is [30] times greater than the starting dose,” Amit Kumar, chairman and CEO of Anixa, said in a company press release. “Although the study is primarily focused on safety at these early, low-dose levels, we have seen promising signs of potential efficacy.”
Trial evaluating five increasing dose levels
Ovarian cancer, which originates in the ovaries, the organs responsible for producing eggs and hormones, is the second most common and the most deadly gynecological cancer, often due to late diagnosis at advanced stages. Standard treatments include surgery and chemotherapy, which may be administered directly into the abdominal cavity to enhance local drug concentration. However, cancer recurrence is common and treatment options are limited at that stage.
CAR T-cell therapy is a form of immunotherapy in which a patient’s T-cells — a type of immune cell — are harvested and genetically modified to express a chimeric antigen receptor (CAR), enabling them to target and attack cancer cells more precisely.
In this study, the engineered CAR T-cells, dubbed FSHCER T cells, are designed to target the follicle-stimulating hormone receptor (FSHR), a molecule found on ovarian cells, as well as on tumor vasculature and various cancer cell types. After expansion in the lab, these modified T-cells are infused back into the patient, either into-the-vein (intravenously) or directly into the abdominal cavity, to seek and destroy cancer cells expressing FSHR.
Preclinical studies in mice implanted with patient-derived ovarian tumors showed FSHR-targeted CAR T-cells reduced tumor progression and improved survival without detectable toxicity.
The Phase 1 trial is evaluating five increasing dose levels, given by intravenous injection or directly into the abdominal cavity in up to 10 participants, to determine the maximum tolerated dose, or the highest dose that can be given safely without causing severe side effects. Secondary objectives include measuring time to disease progression, duration of stable disease, and overall survival for up to 15 years. The trial is currently recruiting at the Moffitt Cancer Center.
