FDA Approves Second Dose of CAR T-Cell Therapy in Ovarian Cancer Trial

• An individual patient investigational new drug application (IND) that allows for the second dose of a chimeric antigen receptor (CAR) T-cell therapy has been approved by the FDA.
• A phase 1 trial (NCT05316129) is evaluating the CAR T-cell therapy for the treatment of recurrent ovarian cancer.
• The follicle stimulating hormone receptor (FSHR)-mediated CAR T technology is also known as chimeric endocrine receptor T-cell (CER-T) therapy.

The FDA has approved an individual patient IND, allowing for a second dose of a novel FSHR-targeting CAR T-cell therapy for the treatment of a patient with recurrent ovarian cancer that may be demonstrating clinical activity to the initial treatment.¹

The CAR T-cell therapy is currently undergoing evaluation in a phase 1 clinical trial at Moffitt Cancer Center for the treatment of patients with recurrent ovarian cancer who have failed standard-of-care therapies.

Six patients have been treated in the first-in-human, dose-escalation trial to date, including 3 in the first cohort and 3 in the second cohort who received triple the dose of CAR T cells compared with those treated in cohort 1. Dose escalation will continue after confirming the previous dosages are safe.

"In the first cohort and at the lowest dose administered, despite an initial increase in tumor size that met criteria for progression, 1 patient has remained off new therapy for many months with no new disease. Even her tumor marker that was initially elevating later began to fall. A biopsy demonstrated tumor with necrosis, inflammation and T-cell infiltration by immunohistochemistry. Based on these findings, we sought approval from the FDA to administer a second treatment to her, aiming to increase the likelihood of a partial or complete response. Recently, we received that approval from the FDA," said Robert Wenham, MD, MS, FACOG, FACS, chair, Department of Gynecologic Oncology at Moffitt Cancer Center, and the principal investigator of the trial, in a press release.¹

The FSHR-mediated CAR T technology is also known as CER-T therapy. It is a novel approach to CAR T-cell therapy that is different from traditional methods through the targeting of FSHR, a receptor that is found on ovarian cells and in the vasculature of tumors.

Gynecologic Cancer Illustration: © Crystal Light - stock.adobe.com

This approach offers new avenues for CAR T-cell therapy through the targeting of hormone receptors, which offers potential benefits in treating ovarian cancer and other FSHR-expressing tumors.

"I am pleased with the very long duration absent of any further disease and the possible response that my patient has exhibited with this innovative therapy, as she had no other realistic options. I look forward to evaluating her progress with successive dosing, as well as future patients who have no other alternatives," said Monica Avila, MD, MPH, gynecologic oncologist at Moffitt Cancer Center, in the press release.

"We were somewhat surprised and quite encouraged to see such a notable response this early, given the low dose in the first cohort. We truly hope we can help this patient, as well as all other women fighting this terrible disease," added Amit Kumar, chief executive officer of Anixa Biosciences, in the press release.

About the Phase 1 Trial

In the phase 1 trial, an estimated 48 patients with a pathologically confirmed diagnosis of high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma that expresses the FSHR antigen will be enrolled if they have received 1 prior platinum-based chemotherapy regimen, are considered refractory to treatment, and have measurable disease.² Other requirements for enrollment include having an ECOG performance status of 2 or better, a life expectancy of at least 3 months, and acceptable bone marrow, renal, and hepatic function.

Additionally, patients with a known germline or somatic BRCA pathogenic mutation must have been previously treated with a PARP inhibitor and subsequently experienced disease progression in order to be enrolled in the study. Patients are eligible if they have received 6 additional prior chemotherapy treatment regimens.

Patients in the study will be treated with 1 infusion of FSHR T cells intraperitoneally or intravenously at the following dose levels: 1 x 10⁵, 3 x 10⁵, 1 x 10⁶, 3 x 10⁶, or 1 x10⁷.

Investigators are identifying the maximum tolerated dose of the FSH-CER T cells as the primary end point. Secondary end points include duration of response, duration of stable disease, and overall survival with this approach. Investigators are also assessing the effect of CER-T on pre-existing antitumor immunity.

REFERENCES:

1. Anixa Biosciences announces FDA approval of individual patient IND for its ovarian cancer CAR-T therapy. News release. Anixa Biosciences, Inc. July 23, 2024. Accessed July 23, 2024. https://tinyurl.com/7wuwpduf

2. Infusion of autologous T cells engineered to target FSH receptor in recurrent ovarian cancer. ClinicalTrials.gov. Updated July 8, 2024. Accessed July 23, 2024. https://clinicaltrials.gov/ct2/show/NCT05316129