Precigen is preparing to launch a Phase 1 trial to test its investigational therapy PRGN-3005 UltraCAR-T for advanced, platinum-resistant ovarian cancer, after the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application.
The open-label, dose-escalation study will assess the treatment’s safety and maximum tolerated dose.
The treatment candidate uses chimeric antigen receptor (CAR) T-cells that are autologous, which means that they originate from the patient’s own immune system. It contains the clinically-validated “Sleeping Beauty” system, which, according to Precigen, enables high-level and stable gene transfer, and contains the cell membrane-bound form of interleukin‐15. This molecule has been shown to promote survival of immune Natural Killer (or NK) cells that have superior anti-tumor properties.
“This patient population has limited treatment options and ovarian cancer remains one of the most challenging with minimal advances in long-term survival for patients with advanced disease,” Mary L. (Nora) Disis, MD, the trial’s lead investigator and a professor of medicine at the University of Washington, said in a press release. “Clinical advancements and new research, including the PRGN-3005 UltraCAR-T study, are needed to make progress in fighting this intractable disease.”
According to Precigen, which is owned by Intrexon Corporation, its UltraCAR-T platform may represent a step forward compared to CAR-T therapy by increasing patient access through a shorter manufacturing time — to less than two days — following gene transfer, and by reducing manufacturing-related costs.
Specifically, UltraCAR-T uses non-viral gene transfer with so-called multigenic vectors to deliver multiple genes, which is intended to improve precision and control of tumor targeting. Also, the approach’s sustained effect after infusion helps avoid T-cell exhaustion, or failure, characterized by loss of anti-tumor function. This is common in viral infections and a cause of resistance to CAR-T therapy.
UltraCAR-T also enables T-cell control by incorporating a kill switch technology for targeted elimination of cells. The manufacturing process eliminates the need for ex vivo propagation — collection of T-cells from a patient to modify and multiply them in the lab — decreasing wait times for patients from weeks to less than two days, Precigen said.
“We are pleased our PRGN-3005 UltraCAR-T investigational therapy received clearance from the FDA to advance into the clinic,” said Helen Sabzevari, PhD, Precigen’s president.
Sabzavari also noted that this is the first such approach to reach clinical trials of solid tumors and that this step is important for patients and Precigen’s team in its “mission of creating innovative medicines with meaningful benefit for patients.”
PRGN-3005 is the second investigational therapy from Precigen to clear its IND application, following the approval of PRGN-3006 UltraCAR-T for patients with relapsed or refractory acute myeloid leukemia and higher risk myelodysplastic syndrome.