Pralsetinib DDI Study in Patients With Advanced or Metastatic Solid Tumors

NCT07704658 | Recruiting Phase 4 FDA Drug

• 1 other identifier: RGL-RET-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

An open-label drug-drug interaction study to evaluate the effects of pralsetinib (Gavreto) on the pharmacokinetics of a CYP450 probe substrate cocktail and, in female participants, a hormonal probe substrate, in participants with rearranged during transfection (RET) fusion- or mutation-positive solid tumors

Conditions

NSCLC (Non-small Cell Lung Cancer); Thyroid Cancer; Solid Tumor Malignancies; Advanced Malignancies

Keywords

Oncology; Drug-Drug Interactions; Medical Oncology; RET Fusion Positive; RET Gene Mutation; Pharmacokinetic (PK)

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-Time Curve from zero to infinity (AUC0-inf)

  To evaluate the effect of pralsetinib on the overall exposure of CYP3A4, CYP2C8, and CYP2C9, probe substrates, and hormonal contraceptive by measuring AUC0-inf for each probe substrate and its relevant metabolites.

  Up to 48 hours post-dose or as appropriate for each probe substrate

• Area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUClast)

  To evaluate the effect of pralsetinib on the overall exposure of CYP3A4, CYP2C8, and CYP2C9 probe substrates, and hormonal contraceptive by measuring AUClast for each probe substrate and its relevant metabolites.

  Up to 48 hours after each probe drug administration

• Maximum Peak Plasma Concentration (Cmax)

  To evaluate how pralsetinib affects the peak levels of probe substrates, and hormonal contraceptive, in the blood after they are taken alone and again after treatment with pralsetinib

  Up to 48 hours after each probe drug administration

Secondary Outcomes (8)

• Time to Maximum Plasma Concentration (tmax)

  Up to 48 hours after each probe drug administration

• Terminal Half-Life (t½)

  Up to 48 hours after each probe drug administration

• Percent of Area Under the plasma concentration-time curve obtained at extrapolation (%AUCex)

  Up to 48 hours after each probe drug administration

• Mean residence time (MRT)

  Up to 48 hours after each probe drug administration

• Terminal Elimination Rate Constant (λz)

  Up to 48 hours after each probe drug administration

Study Arms (1)

Pralsetinib with CYP450 Probe Substrates and Hormonal Contraceptive

EXPERIMENTAL

Drug: Pralsetinib; Drug: CYP3A4, CYP2C8, and CYP2C9 substrates, and hormonal contraceptive

Interventions

Pralsetinib DRUG

Pralsetinib 400mg orally (PO) once daily (QD) from Day 4 to Day 10, with an option to continue up to Day 33

Pralsetinib with CYP450 Probe Substrates and Hormonal Contraceptive

CYP3A4, CYP2C8, and CYP2C9 substrates, and hormonal contraceptive DRUG

Midazolam, repaglinide, and losartan (CYP probe substrates) and, for female participants, estradiol/norethisterone acetate (hormonal probe substrate), administered orally (PO) once on Day 1 and once on Day 9.

Pralsetinib with CYP450 Probe Substrates and Hormonal Contraceptive

Eligibility Criteria

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

You may qualify if:

• Must be willing and able to participate and comply with all study requirements and to provide signed and dated written informed consent
• Adult male or female ≥ 18 years of age at the time of signing the informed consent form.
• Must have a body mass index (BMI) ≥ 18 and ≤ 32 kg/m² and a minimum body weight of 50 kg at screening.
• 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 confirmed diagnosis of advanced or metastatic solid tumor that has relapsed after, or is not responsive to, standard therapies and harbors an oncogenic RET fusion or mutation as determined by a validated test.
• Must have adequate organ function, defined by the following:
• Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L.
• Platelet count ≥ 75 × 10⁹/L.
• Hemoglobin ≥ 9 g/dL.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), or ≤ 5 × ULN in patients with known liver metastases.
• Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN in patients with Gilbert syndrome).
• Creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation.
• Serum phosphorus ≤ 5.5 mg/dL.
• International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) within normal laboratory limits.

You may not qualify if:

• Clinically relevant abnormal medical history, abnormal findings on physical examination, vital signs, electrocardiogram (ECG), or laboratory tests at screening that, in the investigator's judgment, are likely to interfere with the objectives of the trial or the safety of the patient.
• Surgery (e.g., gastric bypass) or medical condition that may significantly affect absorption of study medications, as judged by the investigator.
• History of pneumonitis within the last 12 months.
• History of active or latent tuberculosis (TB), regardless of treatment history, or a positive screening test for latent Mycobacterium tuberculosis infection by QuantiFERON® TB Gold. Indeterminate results may be confirmed by repeat testing or by a purified protein derivative (PPD) skin test.
• 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 safety (e.g., COVID-19 or influenza).
• Clinically significant, uncontrolled cardiovascular disease, including:
• New York Heart Association (NYHA) Class III or IV congestive heart failure.
• Myocardial infarction or unstable angina within the previous 6 months, clinically significant uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., second- or third-degree heart block).
• Uncontrolled hypertension (i.e., mean systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg on 3 repeated measurements) or clinically significant hypotension (i.e., systolic blood pressure \<90 mmHg and/or diastolic blood pressure \<50 mmHg) or severe episodes of orthostatic hypotension.
• History of prolonged QT syndrome or torsades de pointes, or familial history of long QT syndrome.
• QTcF ≥470 ms on at least 2 ECGs performed \>30 minutes apart.
• Central nervous system (CNS) metastases or primary CNS tumor.
• Use of systemic corticosteroids within 4 weeks prior to first dose of study treatment.
• More than 30 Gy of radiotherapy to the lung within 6 months prior to check-in.
• History of multiple and/or severe allergies to drugs or foods, or history of severe anaphylactic reaction.

Sponsors & Collaborators

• Rigel Pharmaceuticals: lead

Study Sites (2)

Hospital Universitario San Pedro

Logroño, La Rioja, 26006, Spain

RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Neoplasms

Interventions

pralsetinib; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP2C8

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

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

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: July 9, 2026
• First Posted: July 15, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)