Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies

A Multi-Center, Open-Label, Drug-Drug Interaction Study to Evaluate the Effect of Olutasidenib on the Pharmacokinetics of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Substrates in Patients With IDH1 Mutation-Positive Malignancies Being Treated With Olutasidenib

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.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Cholangiocarcinoma; Solid Tumor Malignancies; AML (Acute Myeloid Leukemia)
• Intervention / Treatment: Drug: Olutasidenib; Drug: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Probe Substrates

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kay Patel; Phone Number: (650) 624-1100; Email: kpatel@rigel.com
• Study Contact Backup: Name: Jill DeFratis; Phone Number: (650) 624-1100; Email: jdefratis@rigel.com

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • UCI Irvine Health
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • New York Presbyterian Hospital-Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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:

  1. 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.
  2. 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.
• Patients with symptomatic central nervous system metastases or other tumor location (such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention, palliative care, surgery or radiation therapy.
• Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds [msec]) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fridericia's QT correction formula.
• Patients with New York Heart Association Class III or IV heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olutasidenib, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Substrates; 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; 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; Drug: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Probe Substrates; Participants will receive a single dose of each probe substrate on Day 1 and Day 18.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Plasma Concentration (Tmax) of Probe Drugs	To assess how olutasidenib affects the time required to reach peak plasma concentration for each probe drug.	Up to 96 hours after each probe drug administration
Elimination Half-Life (t½) of Probe Drugs	To evaluate the effect of olutasidenib on the terminal elimination half-life of each probe drug.	Up to 96 hours after each probe drug administration
Percent of Area Under the Curve Extrapolated (%AUCex) of Probe Drugs	To determine the proportion of the AUC that is extrapolated, providing insight into olutasidenib's effect on drug elimination.	Up to 96 hours after each probe drug administration
Elimination Rate Constant (λz) of Probe Drugs	To assess how olutasidenib affects the terminal elimination rate constant of each probe drug.	Up to 96 hours after each probe drug administration
Apparent Total Body Clearance (CL/F) of Probe Drugs	To evaluate the effect of olutasidenib on the apparent total body clearance of each probe drug.	Up to 96 hours after each probe drug administration
Apparent Volume of Distribution (Vz/F) of Probe Drugs	To assess how olutasidenib influences the apparent volume of distribution of each probe drug.	Up to 96 hours after each probe drug administration
Incidence, Frequency, and Severity of Treatment-Emergent Adverse Events (TEAEs) with Olutasidenib and Probe Substrates	To assess the safety and tolerability of olutasidenib co-administered with a cocktail of drugs metabolized/transported by CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4, or transported by OATP1B1	From the start of treatment through approximately 30 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: Rigel Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Oncology; Drug-Drug Interactions; IDH1 Mutation; Hematology and Oncology
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Hematologic Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Neoplasms; Leukemia, Myeloid, Acute; Glioma; Cholangiocarcinoma; Amino Acids, Peptides, and Proteins; Proteins; Enzymes; Enzymes and Coenzymes; Oxidoreductases; Cytochromes; Mixed Function Oxygenases; Oxygenases; Hemeproteins; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 2; Oxidoreductases Acting on CH-NH Group Donors; Cytochrome P450 Family 1; Limonene Hydroxylases; Cytochrome P450 Family 3; Oxidoreductases, N-Demethylating; olutasidenib; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A
• Other Study ID Numbers: C-002102-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No