Anixa Biosciences Wraps Up Dosing of Second Cohort in Ovarian Cancer CER-T Trial

Anixa Biosciences has dosed the sixth patient in its phase 1 clinical trial (NCT05316129) evaluating its novel follicle stimulating hormone receptor (FSHR)-targeting chimeric endocrine receptor (CER) T-cell therapy for the treatment of recurrent ovarian cancer.¹ The patient is expected to be the final patient in the trial’s second cohort.

The sixth patient, along with the 2 previous patients in their cohort, was treated at a dose of 3x10⁵ CER T-cells, which is 3 times the dose received by the 3 patients who were treated in the study’s initial cohort (1x10⁵ CER T-cells). Thus far no dose-limiting toxicities (DLT) have been observed among the treated patients in the trial. Provided the sixth patient does not experience a DLT by the time 1 month of safety follow-up has been reached, and the second cohort patients as a whole do not experience new adverse events, Anixa plans to begin enrolling patients for the trial’s third cohort. The third cohort will treat patients at a dose 10 times higher (1x10⁶) than the dose received by patients in the study’s first cohort.

The CER-T therapy is Anixa’s modified chimeric antigen receptor (CAR) T-cell therapy approach using an endocrine receptor (FSHR), which is exclusively expressed at immunologically relevant levels on the granulosa cells of the ovaries, as the target of the engineered T-cells. The clinical trial is being carried out in a collaboration between Anixa and Moffitt Cancer Center.

"We are highly encouraged by the favorable safety profile observed thus far in both the first and second patient cohorts, and are eager to evaluate a higher dose in the next cohort,” Amit Kumar, PhD, the chairman and chief executive officer of Anixa Biosciences, said in a statement.¹ “We are particularly encouraged by a notable response in 1 of the patients in the first cohort, even though the dosage was considered a subtherapeutic level. Our aim is to maintain a positive safety profile as we escalate dosing, with the goal of demonstrating additional objective evidence of efficacy. Unlike conventional CAR-T cell therapies, which have achieved amazing results in various hematological cancers, they have not been effective in solid tumors. In contrast, we believe Anixa's novel technology has the potential to make CAR-T effective in ovarian cancer and perhaps across multiple solid tumor types. Our unique and highly targeted CER-T approach targets the FSHR, which is exclusively expressed on ovarian cells. A potential dual mechanism of action is operating with our therapy targeting tumor vasculature by starving or shrinking the tumor from the inside out, as well as direct targeting of ovarian cells."

Anixa previously announced the dosing of the fifth patient in the trial in May 2024 and the completion of dosing for the first cohort in October 2023.^2,3 Notably, the study, which is expected to enroll approximately 48 participants in total, is evaluating intraperitoneal (IP) delivery against intravenous delivery of the CER T-cells.¹

“We believe thatIP delivery may also be a significant advantage of our therapy, as it allows direct trafficking of the CAR-T cells to the tumor sites, which helps to minimize side effects such as cytokine release syndrome,” Kumar added to the statement.¹ “We believe this method of delivery not only enhances the targeting of the tumor but also improves the overall safety profile of the treatment. We expect that IP delivery may enable us to use dosages that are much higher than possible with intravenous delivery."

In September 2023, CGTLive® interviewed Pamela Garzone, PhD, the chief development officer of Anixa Biosciences, to learn more about the unique aspects of the clinical trial. In addition to evaluating IP delivery, the effect of use or nonuse of lymphodepletion prior to administration is also being assessed.

“We are actually comparing at 1 dose level [the administration of the CER T-cells] with and without lymphodepletion to see if [either approach shows] better expansion, better peak levels, and better persistence of the CARs over time,” Garzone said in the interview. “While there are several proposed mechanisms of why giving preconditioning for solid tumors is a good idea, we're testing that hypothesis within our own trial. So that, to me, is very exciting.”

REFERENCES
1. Anixa Biosciences treats sixth patient in its ovarian cancer CAR-T clinical trial. News release. Anixa Biosciences, Inc. June 24, 2024. Accessed June 25, 2024. https://ir.anixa.com/press-releases/detail/1043/anixa-biosciences-treats-sixth-patient-in-its-ovarian
2. Anixa Biosciences Commences Treatment of Fifth Patient in Ovarian Cancer CAR-T Clinical Trial. News release. Anixa Biosciences, Inc. May 21, 2024. Accessed June 25, 2024.https://ir.anixa.com/press-releases/detail/1042/anixa-biosciences-commences-treatment-of-fifth-patient-in
3. Anixa Biosciences Completes Treatment of First Patient Cohort in Ovarian Cancer CAR-T Clinical Trial. News release. Anixa Biosciences, Inc. October 13, 2023. Accessed June 25, 2024. https://ir.anixa.com/press-releases/detail/1025/anixa-biosciences-completes-treatment-of-first-patient