Rigel Pharmaceuticals, Inc. announced a collaboration with CONNECT, an international collaborative network of pediatric cancer centers, to conduct a Phase 2 clinical trial to evaluate REZLIDHIA®? (olutasidenib) in combination with temozolomide as maintenance therapy in newly diagnosed pediatric and young adult patients with high-grade glioma (HGG) harboring an isocitrate dehydrogenase-1 (IDH1) mutation. Under the collaboration, CONNECT will include olutasidenib in CONNECT's TarGeT-D, a molecularly guided Phase 2rella clinical trial for HGG.

The Rigel-sponsored arm will study post-radiotherapy administration of olutasidenib in combination with Temozolomide followed by olutasidenib monotherapy as maintenance treatment in newly diagnosed pediatric and young adults patients (less than 39 years old) with IDH1 mutation positive HGG, including diffuse intrinsic pontine glioma (DIPG), an aggressive brain tumor with limited treatment options. Rigel will provide funding up to $3 million and study material over the four-year collaboration. This open label Phase 2 trial will be overseen by Drs.

Santosh Valvi and Nicholas Gottardo, Perth Children's Hospital, Dr. Michael J Fisher, Children's Hospital of Philadelphia, and Dr. Maryam Fouladi, Nationwide Children's Hospital, and aims to enroll approximately 60 patients. The primary objective of the olutasidenib arm of the trial is to estimate progression-free survival. The study will also characterize the safety, tolerability, and pharmacokinetics of olutasidenibin pediatric and young adult patients.

The study is estimated to begin enrolling patients in the first half of 2024 and will fulfill Rigel's post-marketing pediatric study requirement related to the FDA approval of REZLIDHIA in relapsed or refractory (R/R) AML. In January 2023, data was published in the peer-reviewed journal Neuro-Oncology from a multicenter, open label, Phase 1b/2 trial of 26 patients with R/R and predominantly enhancing gliomas harboring an IDH1 mutation. The data showed that olutasidenib 150 mg BID was well tolerated and demonstrated preliminary evidence of clinical activity and prolonged disease control in this heavily pretreated population.

The authors noted that olutasidenib is a potent, brain-penetrant, selective inhibitor of mutant IDH1.1 The paper, titled "Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial" can be accessed here. REZLIDHIA is FDA-approved for the treatment of adult patients with R/R acute myeloid leukemia (AML) with a susceptible isocit rate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.