The first patient has been dosed with a novel chimeric antigen receptor (CAR) T-cell therapy in the third cohort of an ongoing phase 1 trial for patients with ovarian cancer. This first-in-human study is evaluating the safety of treatment with autologous T cells genetically modified to express a chimeric endocrine receptor (CER) targeting the follicle-stimulating hormone receptor (FSHR), with or without conditioning chemotherapy, in patients with ovarian cancer.
In the initial cohort which included 3 patients, there were no dose-limiting toxicities (DLT) reported. The same was true for the second 3-patient cohort, where patients were given a CAR T-cell dose triple that of the first cohort. Following the required 1-month observation period to evaluate DLT and review all safety data, the trial has progressed to dosing its first patient in the third cohort. Here, investigators are administering a tenfold increase over the initial dose.
Patients will receive 1 infusion of FSHR T cells at varying dose levels and through different administration methods. For the intraperitoneal treatment arms, patients are being given these T cells at 5 dose levels, with the first group receiving a dose of 1 x 105. The infusion will be delivered through a thin membrane of the abdominal cavity. The second dose level will involve 3 x 105 FSHR T cells, again administered intraperitoneally. The third dose level will increase to 1 x 106 FSHR T cells, followed by a fourth dose level of 3 x 106 FSHR T cells. The fifth dose level will involve the highest dose of 1 x 107 FSHR T cells, all via intraperitoneal infusion.
In the intravenous (IV) treatment arms, patients will receive the FSHR T cells in a similar fashion, given at the same dose levels but administered via IV infusion. Dose Level 1 will involve 1 x 105 FSHR T cells, followed by 3 x 105 at dose level 2. The third dose level will be 1 x 106 FSHR T cells, with the fourth dose level at 3 x 106 cells. The final dose level will consist of 1 x 107 FSHR T cells administered IV.
Enrollment in the study is open to patients 18 years of age and older with a pathologically confirmed diagnosis of high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma. Patient’s disease must be serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated and those with tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements are eligible for enrollment. Further, patients are required to have measurable or detectable disease, carcinoma that expresses the FSHR antigen, an ECOG performance status of 2 or better, a life expectancy of at least 3 months, and adequate bone marrow, renal, and hepatic function.
The primary end point is to determine the maximum tolerated dose of FSHR T cells and secondary end points include duration of response, duration of stable disease, and overall survival.
