Ovarian Cancer CAR-T Clinical Trial Doses First Patient

Article

The novel therapy targets a hormone receptor only expressed at immunologically relevant levels in the ovaries.

The first patient has been treated in the phase 1 clinical trial (NCT05316129) of Anixa Biosciences’ chimeric antigen receptor T-cell (CAR-T) therapy for ovarian cancer, which is being carried out in a partnership with Moffitt Cancer Center.1 

The novel therapy, referred to as chimeric endocrine receptor T-cell (CER-T) therapy, is intended to target the follicle stimulating hormone receptor (FSHR), which is only expressed at immunologically relevant levels in the granulosa cells of the ovaries. Preclinical data on the therapy published in Clinical Cancer Research in 2017 showed that fully murine FSHR-targeted T-cells increased survival without measurable toxicity in immunocompetent mice with syngeneic, orthotopic, and aggressive ovarian tumors.2 Additionally, in an in vivo panel of patient-derived tumors, T-cells expressing full-length FSHR-redirected chimeric receptors led to tumor rejection, among other observed significant therapeutic effects.

“Overall, our study demonstrates the effectiveness and safety of targeting chimeric receptors for T-cell activation using full-length hormones and unveils mechanisms of therapeutic activity that contribute to understanding the effects of adoptively transferred T-cells in ongoing and future clinical trials,” lead author Alfredo Perales-Puchalt, MD, Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, and colleagues concluded.2

The dose-escalation clinical trial aims to recruit up to 48 female patients aged 18 years and older who have a grade 2-3 diagnosis of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma (EOC), including serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated types, but not including pure sarcoma, stromal, or germ-cell tumors. Participants must have carcinoma that expresses the FSHR antigen, and must have had 2 prior chemotherapy regimens, including 1 prior platinum-based chemotherapeutic regimen for ovarian, primary peritoneal, or fallopian tube carcinoma. Participants must also be considered platinum-refractory or platinum-resistant and deemed by the investigator to be unlikely to attain benefit from standard therapies. Patients with an active hepatitis B infection or a history of hepatitis C or HIV, patients with bowel obstruction, and patients with extensive abdominal adhesions that would interfere with port placement or infusion will be excluded from the study.

Participants will receive an infusion between 1x105 and 1x107 of the genetically modified autologous T-cells, delivered either via intraperitoneal or intravenous infusion, depending on which of the 5 dose levels and which arm, respectively, they are assigned to. The primary end point is the maximum tolerated dose. Secondary end points include duration of response, duration of stable disease, and overall survival.

“With limited treatment options for recurrent, chemo-resistant ovarian cancer, I am hopeful that this program can provide a unique opportunity to make a meaningful impact on patients of this devastating disease,” Robert Wenham, MD, MS, FACOG, FACS, lead investigator of the trial and chair of the Department of Gynecologic Oncology at Moffitt Cancer Center, said in a statement regarding the news.1

The single-center study is being conducted at Moffitt Cancer Center in Tampa, Florida, and its expected primary completion date is March 2024.

REFERENCES
1. Anixa Biosciences announces treatment of first patient in its ovarian cancer CAR-T clinical trial. News release. Anixa Biosciences, Inc. August 15, 2022. https://ir.anixa.com/press-releases/detail/999/anixa-biosciences-announces-treatment-of-first-patient-in 
2. Perales-Puchalt A, Svoronos N, Rutkowski MR, et al. Follicle-stimulating hormone receptor is expressed by most ovarian cancer subtypes and is a safe and effective immunotherapeutic target. Clinical Cancer Research. 2017;23(2):441-453. doi.org/10.1158/1078-0432.CCR-16-0492
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