GSK and Ivy Brain Tumor Center Launch Phase 0 Trial of Oral Brain-Penetrant PARP Inhibitor Niraparib for Glioblastoma and Recurrent Glioma

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Recently, GlaxoSmithKline (GSK) and the Ivy Brain Tumor Center announced the initiation of a Phase 0 clinical trial (NCT05076513) to evaluate the efficacy and safety of Zejula (niraparib) in patients with newly diagnosed glioblastoma (GBM) and recurrent glioma (Grade II–IV). Zejula exhibits favorable bioavailability and has demonstrated strong synergistic effects with standard-of-care temozolomide (TMZ) chemotherapy and radiotherapy for glioma across various preclinical studies.

According to the published announcement, this Phase 0 clinical trial will enroll up to 42 patients, divided into two groups: Group A comprises patients with newly diagnosed glioblastoma (GBM), and Group B comprises patients with recurrent glioma harboring IDH mutations and ATRX loss. Initially, 6 patients will be enrolled in Group A to determine the optimal time interval (OTI). The OTI is defined as the interval between the final drug administration and tumor resection surgery, with the timing of surgery determined by when the maximum unbound drug concentration can be detected in the non-gadolinium-enhancing region of the tumor. Following the determination of the OTI, 18 patients will be enrolled in Group A and 18 patients in Group B.

In both cohorts, patients will receive oral Zejula once daily for 4 days prior to the planned surgery to assess drug concentrations in tumor tissue, blood, and cerebrospinal fluid (CSF). Patients in Cohort A whose tumors demonstrate a positive pharmacokinetic (PK) response will proceed to the treatment expansion phase, during which they will receive therapeutic doses of Zejula in combination with standard-of-care fractionated radiotherapy; patients in Cohort B whose tumors demonstrate a positive pharmacodynamic (PD) response will proceed to the treatment expansion phase, during which they will receive Zejula monotherapy until disease progression.

The Ivy Brain Tumor Center is a non-profit translational research program that employs a bold early-phase clinical trial strategy to identify novel therapies for aggressive brain tumors, including glioblastoma (GBM). Its Phase 0 clinical trial program is the largest of its kind globally, enabling personalized therapy in a fraction of the time and cost associated with traditional drug development. Unlike conventional clinical trials that focus on single agents, its accelerated trial program tests combination therapies matched to each individual patient.

Dr. Nader Sanai, Director of the Ivy Brain Tumor Center, stated, “By evaluating PK- and PD-dependent endpoints in Phase 0 clinical trials, brain tumor patients who advance to the expansion phase can be assured that there is biological evidence indicating their tumors can respond to the treatment. If the drug proves ineffective against brain tumors, patients can transition to another treatment or clinical trial without wasting time. This innovative Phase 0 approach streamlines the drug testing and approval process, enabling rapid assessment of glioma patients’ responses to the drug.”

Zejula is a potentially best-in-class PARP inhibitor due to its differentiated efficacy, once-daily dosing, and superior pharmacokinetic profile, including its ability to cross the blood-brain barrier. Developed by GSK, the drug was approved by the US FDA in April 2020 as a maintenance monotherapy for women with advanced ovarian cancer (including epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer) who have achieved a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status.

Currently, GSK is conducting an extensive clinical development program to evaluate the activity of Zejula in treating various tumor types across multiple pivotal clinical trials, including combination regimens of Zejula with other therapies.

Source: Ivy Brain Tumor Center Collaborates with GSK on New Phase 0 Clinical Trial to Evaluate Niraparib in Patients with Brain Cancer