On July 18, 2023 City of Hope, one of the largest cancer research and treatment organizations in the United States and a National Cancer Institute-designated comprehensive cancer Center, and Calidi Biotherapeutics Inc. ("Calidi"), a clinical-stage biotechnology company that is pioneering the development of allogeneic cell-based delivery of oncolytic viruses, reported that the first brain tumor patient was treated at City of Hope in a multicenter, Phase 1 clinical trial evaluating CLD-101, a leading-edge therapeutic candidate in Calidi’s NeuroNova program, comprising tumor-tropic neural stem cells (NSCs) that deliver an oncolytic adenovirus — CRAd-S-pk7 — selectively to tumor sites (Press release, Calidi Biotherapeutics, JUL 18, 2023, View Source [SID1234633282]).
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Calidi holds an exclusive worldwide licensing agreement for patents covering the NSC-CRAd-S-pk7 for its CLD-101 technology. The trial seeks to determine the safety, immunogenicity and preliminary clinical efficacy of treatment with multiple intracerebral doses of CLD-101 in patients with recurrent high-grade glioma.
"The dosing of the first patient in our Phase 1 clinical trial is a significant achievement in our efforts to find new treatment options for patients with brain cancer," said Jana Portnow, M.D., the study’s principal investigator, professor of medical oncology and co-director of City of Hope’s Brain Tumor Program. "Recurrent glioblastoma is notoriously challenging to treat. These are resistant tumor cells that have survived radiation and chemotherapy and spread to other regions of the brain.
"CLD-101 is designed to protect and better distribute the anti-cancer virus to sites of tumors distant from the main tumor mass," Portnow said. "Studies in mice showed that CLD-101 is effective against tumor cells that are resistant to radiation and chemotherapy. We are excited to now assess the safety and potential efficacy of multiple intracerebral doses of CLD-101."
A previously completed Phase 1 dose escalation clinical trial assessed the safety of administering a single dose of CLD-101 into the surgical cavity of newly diagnosed high-grade glioma patients. CLD-101 as an adjunct to standard radiation and temozolomide was well-tolerated and demonstrated safety as well as stimulation of an anti-tumor immune response. These results were published in Lancet Oncology, 2021. Calidi plans to sponsor a Phase 1b/2 trial to further advance CLD-101 treatment of newly diagnosed glioma.
"We have extensive experience using NSCs to deliver anti-cancer payloads selectively to invasive and distant tumor sites. Our research combining NSCs, our studies with oncolytic viruses, as well as a proven track record by City of Hope and Calidi in GMP manufacturing of stem cell and gene therapy products, well positions our City of Hope team to advance the CLD-101 technology in patients," said Karen Aboody, M.D., professor, Department of Stem Cell Biology and Regenerative Medicine, scientific leader of the neuro-oncology disease team at City of Hope and a Calidi advisory board member. "In contrast to the administration of free oncolytic virus, which is rapidly inactivated by the patients’ immune cells, our tumor-targeting NSCs act as a kind of `Trojan horse,’ shielding and protecting the anti-cancer virus en route to tumor sites."
"This allows significantly more virus to reach the tumor sites, generating more tumor cell death and leading to the stimulation of a secondary tumor-specific immune response," Aboody said. "Our goal is to improve clinical outcomes, as well as to decrease the devastating side effects associated with currently available treatments, to improve the patient’s quality of life."
The California Institute for Regenerative Medicine recently awarded a $12 million grant to fund this multicenter, Phase 1 clinical trial. Portnow led the effort resulting in City of Hope becoming part of the National Cancer Institute’s newly formed Glioblastoma Therapeutics Network, a consortium of academic brain tumor centers that collaborate on preclinical and clinical studies to find more efficacious treatments for glioma patients.
"We are pleased to have formed a very productive partnership with City of Hope and look forward to working closely through this critical next step in our CLD-101 development program. Calidi is committed to the clinical advancement of stem cell platforms to deliver oncolytic viruses directly to the main tumor mass and sites of distant tumor, potentially bringing significant therapeutic benefits to cancer patients," said Boris R. Minev, M.D., president, medical and scientific affairs of Calidi Biotherapeutics. "In addition to brain cancer, we are investigating the potential of this novel technology to successfully treat other tumor types as well."
For more information about this trial, click here or contact [email protected] (626) 218-4062.
About CLD-101
The CLD-101 platform, which includes NSC.CRAd-S-pk7, is an allogeneic, "off-the-shelf" therapy comprised of an immortalized NSC line loaded with an engineered oncolytic adenovirus. Upon surgical resection of tumor, NSC-CRAd-S-pk7 is injected into the walls of the resection cavity. The anti-cancer virus it releases is expected to infect and kill any remaining tumor cells. A second mechanism of cytoxicity is that the oncolytic virus can elicit a tumor-specific immune response from the patient. Calidi holds an exclusive worldwide licensing agreement covering the NSC-CRAd-S-pk7 technology.