FDA clears application for anti-PD-1 CAR-T to treat hematologic, breast cancers
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The FDA cleared an investigational new drug application for PRGN-3007, a chimeric antigen receptor T-cell therapy for patients with advanced hematologic malignancies or solid tumors that express receptor tyrosine kinase-like orphan receptor 1.
PRGN-3007 (Precigen) is a gene-edited autologous CAR T-cell therapy that targets the protein receptor tyrosine kinase-like orphan receptor 1 (ROR1) on the surface of cancer cells. The agent was developed using Precigen’s UltraCAR-T therapeutic platform, designed to eliminate ex vivo expansion and reduce manufacturing time.
The multigenic CAR T-cell therapy expresses a ROR1-targeted CAR, membrane-bound interleukin-15, a kill switch intended to provide greater precision and control for disease targeting, and a novel intrinsic PD-1 blockade that negates the need for a second immunotherapy agent.
“This is the first study of our next-generation UltraCAR-T, which adds checkpoint blockade to our nonviral, multigenic UltraCAR-T platform,” Helen Sabzevari, PhD, president and CEO of Precigen, said in a company-issued press release.
“PRGN-3007 eliminates the need to combine an antigen-specific CAR-T with a separate checkpoint inhibitor, which has the potential to avoid systemic toxicity and reduce cost,” she added. “This new study is a big step toward our UltraCAR-T library approach, which aims to deliver personalized autologous UltraCAR-T therapies based on a patient's cancer indication and biomarker profile using overnight manufacturing at the patient's medical center.”
The IND clearance will allow Precigen to start enrollment for a clinical trial to evaluate the safety and efficacy of PRGN-3007 for patients with ROR1-positive hematologic and solid tumors. Arm 1 of the study will include patients with relapsed or refractory chronic lymphocytic leukemia, mantle cell lymphoma, acute lymphoblastic leukemia or diffuse large B-cell lymphoma. Arm 2 is planned for patients with locally advanced unresectable or metastatic histologically confirmed triple-negative breast cancer.
The phase 1/phase 1b dose-escalation study of PRGN–3007 will be conducted in collaboration with Moffitt Cancer Center.
“ROR1 is an attractive target for treatment of multiple [hematologic] and solid tumors due to its high expression in cancer and minimal expression in healthy adult tissues,” Javier Pinilla-Ibarz, MD, PhD, senior member in the lymphoma section at Moffitt Cancer Center and principal investigator for the PRGN-3007 clinical study, said in the release. “Preclinical studies of PRGN-3007 UltraCAR-T indicate the potential for improved efficacy by specific targeting of ROR1 combined with intrinsic blockade of PD-1 expression, and we look forward to investigating the potential in this first-in-human clinical study.”
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