Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies

NCT07486713 | Recruiting Phase 4 FDA Drug

• 1 other identifier: C-002102-003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

A open-label drug-drug interaction (DDI) study to evaluate the effects of olutasidenib on the pharmacokinetics (PK) of a CYP450 and OATP1B1 probe substrate cocktail in participants with IDH1 mutation-positive malignancies.

Conditions

AML (Acute Myeloid Leukemia); Glioma; Cholangiocarcinoma; Solid Tumor Malignancies

Keywords

IDH1 Mutation; Hematology and Oncology; Oncology; Drug-Drug Interactions

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-Time Curve (AUC) of Probe Drugs

  To evaluate how olutasidenib affects the overall exposure of several test drugs (probe substrates) that are used to measure the activity of certain enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4) and a drug transporter (OATP1B1). This will be assessed by measuring the area under the plasma concentration-time curve after the probe drugs are taken alone and again after treatment with olutasidenib.

  Up to 96 hours after each probe drug administration.

• Maximum Plasma Concentration (Cmax) of Probe Drugs

  To evaluate how olutasidenib affects the peak levels of probe drugs in the blood after they are taken alone and again after treatment with olutasidenib.

  Up to 96 hours after each probe drug administration.

Secondary Outcomes (7)

• Time to Maximum Plasma Concentration (Tmax) of Probe Drugs

  Up to 96 hours after each probe drug administration

• Elimination Half-Life (t½) of Probe Drugs

  Up to 96 hours after each probe drug administration

• Percent of Area Under the Curve Extrapolated (%AUCex) of Probe Drugs

  Up to 96 hours after each probe drug administration

• Elimination Rate Constant (λz) of Probe Drugs

  Up to 96 hours after each probe drug administration

• Apparent Total Body Clearance (CL/F) of Probe Drugs

  Up to 96 hours after each probe drug administration

Study Arms (1)

Olutasidenib, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Substrates

EXPERIMENTAL

Participants will receive olutasidenib twice daily from Day 5 to Day 22. Participant will also receive a single dose of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 probe substrates on Day 1 and Day 18.

Drug: Olutasidenib; Drug: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Probe Substrates

Interventions

Olutasidenib DRUG

Participants will receive repeated dosing of olutasidenib from Day 5 to Day 22 until steady state, with an option to continue treatment up to Day 64

Olutasidenib, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Substrates

CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Probe Substrates DRUG

Participants will receive a single dose of each probe substrate on Day 1 and Day 18.

Olutasidenib, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Substrates

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female ≥ 18 years of age at the time of signing the informed consent form
• Must have an Eastern Cooperative Oncology Group performance status ≤ 2.
• Must have recovered from the non-hematologic toxic effects of prior treatment to Grade ≤ 1, or baseline value (excluding infertility, alopecia, or Grade 1 neuropathy)
• Must have a diagnosis of IDH1m+ malignancy to be treated with olutasidenib (e.g. acute myeloid leukemia \[AML\], gastrointestinal \[GI\] cancers, glioma). Patient should not have received olutasidenib within the 2 weeks prior to the first dose of study drug.
• Patient must have an adequate organ function, defined by the following:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values ≤ 2.5 × upper limit of normal (ULN).
• Bilirubin ≤ 1.5× ULN (≤ 3 × ULN in patients with Gilbert Syndrome) or ≤ 3 × ULN for patients with AML involvement.
• Creatinine clearance ≥ 30 mL/min using Cockcroft-Gault equation.
• Female patients who are women of childbearing potential (WOCBP) must have a negative serum (β-hCG) pregnancy test at screening and negative urine test (positive urine tests are to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug. WOCBP are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
• WOCBP, must agree to use two methods of birth control (e.g. hormonal and a barrier method such as a condom), or must be considered highly unlikely to conceive during the dosing period and for 3 months after last study treatment.
• Male patients with female partners of childbearing potential may be enrolled if they both agree to use highly effective methods of contraception during the dosing period and for 3 months after last study treatment.
• Male patients must refrain from donating sperm during the dosing period and for 3 months after last study treatment.

You may not qualify if:

• Female patients who are pregnant or breastfeeding.
• Patients who are active smokers. Those who have ceased smoking \> 1 month before the Screening Visit will be allowed.
• Ingestion of alcohol within 72 hours prior to first study drug administration and during the study period.
• Any patient's who plans to become pregnant or father a child (including ova or sperm donation) while enrolled in this study or within 3 months after last dose of study drug.
• Known allergy or history of hypersensitivity to study drugs or their excipients.
• Human immunodeficiency virus (HIV) positivity.
• Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or by RNA polymerase chain reaction (PCR) at screening.
• Any patient's with a serious infection requiring intravenous or systemic antibiotics within 7 days prior to initiation of study treatment, or any active infection that, in the opinion of the Investigator, could impact patient's safety (e.g. COVID-19).
• Use of concomitant medications that are moderate or strong CYP1A2, 2B6, 2C8, 2C9, 2C19, and/or 3A4 inhibitors within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
• Use of concomitant medications that are moderate or strong CYP1A2, 2B6, 2C8, 2C9, 2C19, and/or 3A4 inducers within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion (or following review by the Sponsor), could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
• If less than the minimum time has elapsed from prior anticancer treatment to first dose of study treatment as follows:
• Cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors, or major surgery within 4 weeks prior to the first scheduled study treatment; for longer acting agents such as nitrosourea, mitomycin or antibody therapies, a minimum of 6 weeks.
• Use of investigational agents within 4 weeks prior to study enrollment (within 6 weeks if the treatment was with a long-acting agent).
• History of prior second malignancy unless disease-free for ≥ 12 months or considered surgically cured. Patients with nonmelanoma skin cancers or with carcinomas in situ at any time following curative intent surgery and low grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to the study, or previously resected are also eligible.

Sponsors & Collaborators

• Rigel Pharmaceuticals: lead

Study Sites (2)

UCI Irvine Health

Orange, California, 92868, United States

RECRUITING

New York Presbyterian Hospital-Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Glioma; Cholangiocarcinoma; Neoplasms

Interventions

olutasidenib; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma

Intervention Hierarchy (Ancestors)

Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 Enzyme System; Cytochromes; Enzymes and Coenzymes; Cytochrome P450 Family 1; Mixed Function Oxygenases; Oxygenases; Oxidoreductases; Enzymes; Hemeproteins; Proteins; Amino Acids, Peptides, and Proteins; Cytochrome P450 Family 2; Limonene Hydroxylases; Cytochrome P450 Family 3; Oxidoreductases, N-Demethylating; Oxidoreductases Acting on CH-NH Group Donors

Central Study Contacts

Kay Patel

CONTACT

(650) 624-1100; kpatel@rigel.com

Jill DeFratis

CONTACT

(650) 624-1100; jdefratis@rigel.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: March 20, 2026
• Study Start: February 23, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)