Study of Olutasidenib and Temozolomide in HGG

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age12 Years to 39 Years
• SexAll
• Healthy volunteersNo

You may be able to join if

• Criteria TarGeT-D study strata definitions
• Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.
• Stratum B: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.
• Stratum C: Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.
• Inclusion Criteria:
• Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• 1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis:
• Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.
• For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma.
• All other HGG must be WHO Grade 3 or 4.
• 3) Disease status: There are no disease status requirements for enrollment
• Measurable disease is not required. Patients without measurable disease are eligible.
• Primary spinal tumor: Patients with a primary spinal HGG are eligible.
• Patient must not have metastatic disease.
• Inclusion criteria for assignment to TarGeT-D, for all strata:
• 1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here:
• R132H, R132C, R132S, R132G or R132L.
• Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee.
• Patients with IDH2 mutations are not eligible.
• Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• 2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.
• 3 Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• 4 Prior Therapy 2.4.1 Surgery, radiation, and/or dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.
• 4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.
• 4.3 Timing between diagnosis and start of RT: Patients must have started RT < 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.
• Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT.
• Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.
• 5 Organ Function Requirements 2.5.1 Adequate Bone Marrow Function Defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3.
• Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• Hemoglobin > 8 g/dL (may be transfused). 2.5.2 Adequate Renal Function Defined as
• Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR
• Maximum serum creatinine based on age/gender as follows: 10 to < 13 yrs=1.2 mg/dL for males and females. 13 to < 16 yrs=1.5 mg/dL for males and 1.4 mg/dL for females.
• 5.3 Adequate Liver Function Defined as:
• Total bilirubin must be ≤ 1.5 × institutional ULN.
• AST(SGOT)/ALT(SGPT) < 3 × institutional ULN.
• Alkaline Phosphatase < 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as:
• Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4/5.
• Patients must be able to swallow oral medications to be eligible for study enrollment.
• 6. Informed consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

You cannot join if

• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy.
• A highly effective contraception method is defined as one that results in a low failure rate (<1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:
• Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.
• Progesterone-only hormonal contraception associated with inhibition of ovulation.
• Intra Uterine Device (IUD).
• Intra uterine hormone releasing system.
• Bilateral tubal occlusion.
• Vasectomized partner.
• Sexual abstinence (avoiding heterosexual intercourse).
• The following contraceptive measures are NOT considered effective:
• Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation.
• Male or female condom with or without spermicide.
• Cap, diaphragm, or sponge with spermicide.
• Using the following types of concomitant medications:
• Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.
• Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
• Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D.
• Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4/5 are not eligible.
• Strong CYP3A4/5 inducers: Patients who are receiving strong inducers of CYP3A4/5 are not eligible. Strong inducers of CYP3A4/5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study.
• Patients who are receiving medications known to prolong QTc interval are not eligible
• Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.
• Other Criteria
• Infection: Patients who have an uncontrolled infection are not eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.
• Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history.
• Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible.
• Patients with any prior solid organ transplant are not eligible.
• Patients with secondary/radiation-related HGG are not eligible.
• Patients with metastatic/disseminated HGG who have received CSI are not eligible.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

olutasidenib. An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble) with a mutation at arginine (R) 132, IDH1(R132), with potential antineoplastic activity. Upon administration, olutasidenib specifically inhibits IDH1(R132), thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH(R132). IDH1(R132) mutations are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG. NCI Drug Dictionary

locally-acting temozolomide formulation SI-053. A powder for gel formulation containing the cytotoxic alkylating agent temozolomide (TMZ), an imidazotetrazine derivative of the alkylating agent dacarbazine, immobilized on the polymeric carrier dextran phosphate, with potential antineoplastic activity. The TMZ formulation SI-053 forms a viscous gel upon reconstitution in water. Upon local intraoperative administration of the gel into the cavity that is formed after resection of the brain tumor, SI-053 allows for local and prolonged action of TMZ. TMZ is converted at physiologic pH to the short-lived active compound 5-(3-methyl-(triazen-1-yl)-imidazole)-4-carboxamide (monomethyltriazenoimidazole carboxamide; MTIC). The cytotoxicity of MTIC is due to methylation of DNA, particularly at the O6 and N7 positions of guanine residues, resulting in cell cycle arrest, inhibition of DNA replication and the induction of apoptosis. The local administration of TMZ allows for the local destruction of the remaining tumor cells immediately after the removal of the tumor and may prevent the recurrence of tumor growth while having no severe systemic toxicity. NCI Drug Dictionary

Treatments listed in the registry

• Olutasidenib + TMZ (Drug): Olutasidenib 150 mg PO BID + Temozolomide 200 mg/m2 PO QD

Non Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• radiation: Part of the study plan

Main goals

• Establish the RP2D of Olutasidenib and Temozolomide (Feasibility cohort) (Completion of cycle 1 (28 days) for 6-24 patients)
• Assess Progression-Free Survival (PFS) in Grade 3 IDH1-mutant Astrocytoma (Stratum A) (From date of diagnosis until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up 24 months)
• Maximum plasma concentration [Cmax] of Olutasidenib (From Day 1 of treatment until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months)

Other goals

• Evaluate objective response rate (ORR) in HGG (All Strata)
• Evaluate Health-Related Quality of Life Outcomes (All Strata)
• Evaluate Overall Survival in IDH1-mutant Grade 3 Astrocytoma (Stratum A)
• Assess Progression-Free Survival in IDH1-mutant Grade 4 Astrocytoma (Stratum B)

Planned enrollment: 60 (estimated).

• University of Miami Hospital and Clinics, Miami, Florida
• Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
• Duke University Health System, Durham, North Carolina
• Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
• Nationwide Children's Hospital, Columbus, Ohio
• Seattle Children's Hospital, Seattle, Washington

2 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06161974
• NCI Drug Dictionary: C129687
• NCI Drug Dictionary: C1244

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Aug 31, 2026. Public record; not medical advice.