Phase 1b/2 trial of CLD-101 for aggressive glioma now recruiting
Trial in Chicago seeks up to 20 newly diagnosed adults to test multiple doses
Calidi Biotherapeutics has begun recruiting adults with high-grade glioma for a Phase 1b/2 clinical trial to study the effects of multiple doses of its experimental therapy CLD-101.
The trial (NCT06169280) will assess the safety and feasibility of administering multiple doses of the treatment, in up to 20 patients recruited at the Northwestern University/Northwestern Memorial Hospital, in Chicago.
It builds on data from a previous Phase 1 trial that showed the treatment was generally safe, with patients achieving a median survival of 1.5 years. The trial also allowed researchers to identify an optimal dose to be administered to patients in the current study.
“Should the results of this trial demonstrate treatment outcomes consistent with the previous study, now in a larger patient group and with multiple doses of CLD-101, the implications could be transformative for the treatment of brain tumors,” Allan Camaisa, Calidi’s CEO and chairman, said in a company press release.
Gliomas are brain tumors caused by the abnormal growth of glial cells, which are cells that support nerve function in the central nervous system (the brain and spinal cord). Malignant gliomas have a very poor prognosis, with patients typically surviving for a few months after diagnosis.
CLD-101 combines neural stem cells with engineered oncolytic adenovirus
CLD-101, also known as NSC-CRAd-S-pk7, is a treatment approach that combines the potential of neural stem cells (NSCs), which have the ability to develop into various central nervous system cell types, loaded with an engineered oncolytic adenovirus. This modified virus is designed to selectively replicate within and destroy cancer cells.
The treatment was previously tested in an open-label Phase 1 trial (NCT03072134) that enrolled 12 adults with newly diagnosed high-grade, or more aggressive (grade 3 and 4), glioma. After surgery to remove the tumor, CLD-101 was injected into the walls of the resection cavity.
A first group of patients received 5 × 107 NSCs containing a total dose of 6.25 billion viral particles, a second group received 1×108 NSCs containing 12.5 billion viral particles, while a third group received 1.5×108 NSCs containing 18.75 billion viral particles.
Within 10 to 14 days, patients started treatment with temozolomide, an anti-cancer medication for serious brain cancers, and radiotherapy, and were followed up for a median of 18 months (1.5 years).
Results showed patients achieved a median progression-free survival of 9.1 months and a median survival of 18.4 months. Of note, progression-free survival refers to the length of time during and after treatment that a patient lives without their disease worsening or progressing.
Treatment found to be safe
The treatment was found to be safe, with no treatment-related deaths. One patient in the highest dose group developed meningitis, which is an inflammation of the protective membranes covering the brain and spinal cord, due to a problem with the treatment administration.
As no dose-limiting toxicity was reached, the highest dose was selected to be used in the new Phase 1b/2 trial, which will assess whether multiple doses of CLD-101 are safe and if they can influence a patient’s response to treatment, overall survival, time to tumor progression, and quality of life.
After a biopsy confirms high-grade glioma, patients will receive the first treatment dose, followed by surgery about two weeks later to remove the tumor and administer the second CLD-101 dose. Two weeks after surgery, patients will start radiation and chemotherapy (chemoradiation) and receive a third CLD-101 dose two weeks after that. A fourth dose will be administered four weeks later, at the end of chemoradiation.
After finishing radiation, patients will receive chemotherapy and tumor-treating fields, as well as two additional doses of the treatment every four weeks.
“I am extremely excited about the commencement of recruitment for the multiple-dose CLD-101 trial in newly diagnosed [high-grade glioma] patients. This increases the probability of success due to the improved treatment regimen initiated as early as possible,” said Maciej Lesniak, MD, chairman of the department of neurological surgery at Northwestern University, and a researcher in the trial.
The trial was granted funding by the National Cancer Institute, part of the National Institutes of Health.
