The company noted that there have been no dose-limiting toxicities so far among the 3 patients in the cohort.
Anixa Biosciences has finished the dosing of patients in the first cohort of its phase 1 clinical trial (NCT05316129) evaluating the novel follicle stimulating hormone receptor (FSHR)-targeting chimeric endocrine receptor (CER) T-cell therapy for the treatment of recurrent ovarian cancer.1
The company noted that there have been no dose-limiting toxicities so far among the 3 patients in the cohort, who each were treated at a dose of 1x105 CER T-cells. Pending a review of safety data from these patients, set to take place after enough time has passed since the dosing of the final patient in the cohort, Anixa intends to initiate enrollment of the trial’s second cohort right away. Patients in the second cohort will be treated with a dose of 3x105 CER T-cells. The trial is being carried out in a collaboration between Anixa and Moffit Cancer Center.
"We are very pleased with the results to date,” Robert Wenham, MD, MS, FACOG, FACS, the principal investigator of the trial, and the head of gynecological oncology at Moffitt, said in a statement.1 “The first 3 patients were dosed through a peritoneal catheter and no patient has had a dose-limiting toxicity. Since most lesions in ovarian cancer are within the peritoneum, we hope the delivered CAR-T cells remain localized and active in the vicinity of the tumors. It's possible that we may see very limited side effects due to this local, as opposed to systemic, delivery. The very selective target also gives us reason to hope that on-target, off-tumor effects will not be prevalent as in other solid tumor studies. Perhaps this delivery approach may enhance efficacy as well. However, we will also test this therapy by intravenous administration, in patients for whom peritoneal administration is not possible."
The CER-T therapy is Anixa’s modified chimeric antigen receptor (CAR) T-cell therapy approach using an endocrine receptor as the target of the engineered T-cells. Anixa developed this approach to tackle preexisting difficulties with CAR T-cell therapies in solid tumors. The trial, which is taking place at Moffit in Tampa, Florida, is recruiting women aged 18 years and older who have progressing ovarian cancer for which at least 2 previous therapies were not successful in treating the disease. Anixa noted that despite the minimum requirement, many of the patients have disease that has not responded to more than 2 previous therapies.
In September 2023, following an update on the status of the clinical trial presented by Anixa at the 8th Annual CAR-TCR Summit, held August 29-September 1, 2023, in Boston, Massachusetts, CGTLive™ interviewed Pamela Garzone, PhD, the chief development officer of Anixa Biosciences. Garzone spoke more in depth about the unique aspects of the clinical trial, which include evaluating intraperitoneal delivery against intravenous delivery for the therapy and the effect of use or nonuse of lymphodepletion prior to administration. She also discussed the challenges of applying CAR-T to the solid tumor field more generally, specifically honing in on antigen selection and homing/infiltration of T-cells. She noted that FSHR was selected as the target for Anixa’s FSHCER T-cells for several advantageous factors, such as the fact that in healthy tissue it is only expressed in the ovaries and testes.
“We are actually comparing at 1 dose level [the administration of the FSHCER 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.”