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Label indication Relapsed or Refractory Acute Myeloid Leukemia REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14.1 )] . FDA label
Also known as Olutasidenib Investigational Agent Administration
Olutasidenib · 4 trials · 21 indications
The number of participants experiencing excessive toxicity in six (6) patient safety lead-in over the duration of study treatment will be reported. All treatment-emergent adverse events (TEAEs) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Composite complete remission (CRc) among participants will be reported as a percentage. CRc is includes number of participants experiencing complete remission \[CR\], complete remission with partial hematologic recovery \[CRh\] or complete remission with incomplete hematologic recovery \[CRi\] after up to 3 cycles as defined by modified 2022 European LeukemiaNet (ELN) criteria.
Composite complete remission (CRc) rate is defined as patients that meet the criteria for CR + CRh + CRi per the modified European LeukemiaNet (mELN) 2022. * Complete Remission (CR) is defined as absence of leukemia cells in the bone marrow (\< 5% blasts), normal blood counts (absolute neutrophil count ≥ 1000/μL and platelet count ≥ 100,000/μL), and the absence of circulating blasts, and extramedullary disease * Complete Remission with Hematologic recovery (CRh) is defined as meeting all criteria for CR as Bone marrow myeloblasts \< 5%; absence of circulating blasts; absence of extramedullary disease; both ANC ≥ 0.5x109/L (500/µL) and platelet count ≥ 50×109/L (50 000/µL) * Complete Remission with Incomplete hematologic recovery (CRi) is defined as meeting all criteria for Complete Remission (CR) except for either a low neutrophil count (neutropenia) or a low platelet count (thrombocytopenia)
To identify the dose of olutasidenib that is feasible when given post-RT in combination with temozolomide as maintenance therapy in pediatric and young adult patients newly diagnosed with IDH1-mutant high-grade glioma
To assess the post-RT efficacy of olutasidenib in newly diagnosed patients with WHO Grade 3 IDH1-mutant Astrocytoma treated with maintenance olutasidenib and temozolomide for 13 cycles followed by 13 cycles of single agent olutasidenib compared to molecularly-stratified and matched historical controls
To characterize the plasma pharmacokinetic (PK) properties of olutasidenib in pediatric patients (e.g., 12 to \< 18 years of age), administered in combination with temozolomide (first year) and as single agent (second year) as maintenance chemotherapy by measuring the Maximum Concentration \[Cmax\] and Area Under the Curve (AUC) of olutasidenib in plasma (All strata).
Feasibility defined as the number of participants with 75% protocol treatment compliance for a duration of at least 4 cycles (to include protocol defined dose delays), or until disease relapse or allogeneic hematopoietic stem cell transplant (alloHCT).
Incidence of grade ≥4 adverse events (AEs) attributable to study drug for duration of treatment on study
| Arm | Type | Description |
|---|---|---|
| OLUVENAZA Treatment Group | EXPERIMENTAL | Participants in this group will receive combination treatment of Olutasidenib, Venetoclax and Azacitidine orally for up to 12 cycles, each cycle lasting 28 days. Total participation duration is about 14 months |
| Olutasidenib and Azacitidine | EXPERIMENTAL | Each cycle will last for 28 days. Patients will receive olutasidenib 150 mg orally twice daily Day 1 through Day 28. After 3 cycles of olutasidenib, azacitidine 75 mg/m2 given on Day 1 through Day 7 may be added at the discretion of the treating investigator if the patient has not achieved a complete remission or for whom loss of response is suspected. Subjects with at least a PR after 6 cycles of treatment will continue treatment.. Subjects without at least a PR after 6 cycles of treatment will move to long term follow up. |
| Stratum A | EXPERIMENTAL | Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3. |
| Stratum B | EXPERIMENTAL | Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4. |
| Stratum C | EXPERIMENTAL | Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG. |
| Olutasidenib Investigational Agent Administration | EXPERIMENTAL | 150 mg by mouth twice daily. |
| Name | Type | Description |
|---|---|---|
| Olutasidenib | DRUG | Olutasidenib will be supplied as 150 mg capsules to be administered orally, twice per day (BID) on an empty stomach (fasting at least 1 hour before or 2 hours after a meal), starting on Cycle 1 Day 1, and will be given continuously. |
| Venetoclax | DRUG | Participants will receive Venetoclax as a 100mg tablet to be self-administered orally with a meal and water once daily, two hours after starting Olutasidenib administration, starting on Cycle 1 Day 1. The dosing regimen of Venetoclax is as follows: * Cycle 1: Days 1 - 21 over a 28-day cycle * Cycle 1 Week 1: Ramp-up dosing schedule up to 400mg (4 x 100mg/tablet) * For participants with blast clearance: Cycle 2 and beyond: Days 1 - 14 over a 28-day cycle * For participants with persistent clearance: Cycle 2 through 4: Days 1 - 21 |
| Azacitidine | DRUG | Participants will receive Azacitidine 75 mg/m2 per day via subcutaneous (SC) injection or intravenous (IV) infusion on Days 1-7 of each cycle. |
| Azacitidine (AZA) | DRUG | Azacitidine 75 mg/m2 subcutaneously or IV (over 10-40 minutes) |
| Olutasidenib + TMZ | DRUG | Olutasidenib 150 mg PO BID + Temozolomide 200 mg/m2 PO QD |
| Olutasidenib Investigational Agent Administration | DRUG | Twice daily olutasidenib maintenance therapy |
Inclusion Criteria: 1. Participant is an adult male or female participant aged 18-75 years considered eligible to undergo intensive induction chemotherapy at the time of signing the informed consent form (ICF). 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 3. Confirmed diagnosi...
Olutasidenib is an investigational small molecule IDH1 inhibitor being developed by Rigel Pharmaceuticals, Inc. (ticker RIGL). It is in Phase 2 clinical development for IDH1-mutated cancers, including acute myeloid leukemia and high grade glioma. It is a targeted therapy that selects for patients whose tumors carry an IDH1 mutation.
Olutasidenib is being studied for IDH1-mutated acute myeloid leukemia and for high grade glioma, including astrocytoma, oligodendroglioma, diffuse midline glioma, and other IDH1-mutant brain tumors. It is also being tested in relapsed or refractory AML and in newly diagnosed AML, including combinations with venetoclax, azacitidine, and temozolomide.
Olutasidenib targets mutant IDH1, the isocitrate dehydrogenase 1 enzyme. It acts as an IDH1 inhibitor, binding the mutated enzyme to block the abnormal metabolic activity driven by IDH1 mutations such as R132C, R132H, R132S, R132G, and R132L. This makes it a biomarker-selected therapy for tumors carrying those mutations.
Olutasidenib is developed by Rigel Pharmaceuticals, Inc., which trades on Nasdaq under the ticker RIGL. Rigel is the sponsor of the clinical program evaluating olutasidenib as a single agent and in combination regimens for IDH1-mutated acute myeloid leukemia and high grade glioma.
Olutasidenib is in Phase 2 clinical development. It is an investigational agent and has not been established as approved for the indications under study. The program includes Phase 1 and Phase 2 trials, with active studies in IDH1-mutated acute myeloid leukemia and in high grade glioma.
Olutasidenib is being studied in NCT07471841 in relapsed IDH1-mutated AML after venetoclax, NCT07130695 as single and combination therapy in IDH1-mutant AML after induction and consolidation, NCT06782542 with venetoclax and azacitidine in newly diagnosed IDH1-mutated AML, and NCT06161974 with temozolomide in high grade glioma.