Anixa Biosciences, in collaboration with Moffitt Cancer Center, has submitted a protocol amendment to the FDA seeking approval for repeat dosing of its novel chimeric endocrine receptor (CER) T-cell therapy in an ongoing Phase 1 clinical trial (NCT05316129) for ovarian cancer. This amendment aims to enable the administration of second doses to patients who may benefit from the treatment, streamlining the process and potentially enhancing therapeutic outcomes.
The CER-T therapy targets the follicle stimulating hormone receptor (FSHR), which is selectively expressed on ovarian granulosa cells. The Phase 1 trial is evaluating both intraperitoneal and intravenous delivery methods of the CER-T cells in patients with recurrent ovarian cancer who have not responded to standard-of-care therapies. The trial aims to enroll approximately 48 participants.
Rationale for Repeat Dosing
The decision to seek approval for repeat dosing was influenced by the observation of clinical activity in a patient who received a single dose of the CER-T therapy. A tumor biopsy revealed cellular infiltration and necrosis, suggesting that the therapy had produced a biological effect. While the patient initially met the criteria for disease progression based on tumor size, their cancer has since remained relatively stable without additional therapy since the first infusion.
Robert Wenham, MD, MS, FACOG, FACS, chair of the Gynecologic Oncology Department at Moffitt and principal investigator of the trial, stated, "In initial phase 1 clinical trials, it is customary to begin with low, often subtherapeutic cell doses to verify safety, before increasing the dose levels. In our study, the patient approved for a second dose by the individual IND received the starting, lowest dose. While initially meeting the criteria for progression due to size of her predominate tumor, her cancer has since remained relatively stable and she has not received additional therapy since her first infusion. We are hoping a second, higher dose may improve her overall response and outcome. In general, we anticipate that higher cell doses will lead to efficacy, but for solid tumors, a second dose may be needed in a subset of patients to improve the rate and durability of responses."
Trial Progress and Safety Profile
To date, six patients have been treated in the trial. Three patients received a dose of 1x10^5 CER T-cells (cohort 1), and three patients received a dose of 3x10^5 CER T-cells (cohort 2). According to a June 2024 update, no dose-limiting toxicities (DLT) have been observed among the treated patients.
Amit Kumar, PhD, chairman and chief executive officer of Anixa Biosciences, commented, "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. 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."
Potential of CER-T Therapy
Anixa Biosciences believes that its CER-T therapy has the potential to overcome the limitations of conventional CAR-T cell therapies in solid tumors. The unique approach targets FSHR, which is exclusively expressed on ovarian cells, potentially offering a dual mechanism of action by targeting both tumor vasculature and ovarian cells directly.
Dr. Kumar added, "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."
