A Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer Patients

Phase 1

Withdrawn

• Conditions: Locally Advanced Solid Tumor; Metastatic Solid Tumor
• Interventions: Drug: repotrectinib (TPX-0005)

• Registration Number: NCT05828277
• Lead Sponsor: Turning Point Therapeutics, Inc.

Brief Summary

This is a Phase 1 study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib in patients with advanced cancer.

Detailed Description

This is a Phase 1, multicenter, multiple-dose, open-label, nonrandomized study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib following single and multiple dose administration of repotrectinib in patients with advanced cancer. This study will enroll 8 patients each with moderate hepatic impairment, severe hepatic impairment and normal hepatic function.

Study Timeline

• Study Start: 2022-07-28
• Study First Submitted: 2023-03-28
• Study First Submitted QC: 2023-04-12
• Study First Posted: 2023-04-25
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-26
• Primary Completion: 2025-08-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor for which standard curative or palliative measures do not exist or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least 1 of the following:

   1. The presence of at least 1 lesion, measuring ≥2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.
   2. The presence of liver lesion(s) (as defined in inclusion criteria 3a) with alphafetoprotein ≥ 400 ng/mL.
   3. Tissue confirmation.

2. For patients with genetic ROS1 or NTRK 1-3 gene fusion, tissue-based local testing should be documented.

3. Biliary obstruction for whom a biliary drain or stent has been placed are eligible.

4. Eastern Cooperative Oncology Group Performance Status scores 0 to 2.

5. The patient must have no clinically significant change in hepatic disease status within the last 30 days before screening.

6. Patient with ascites must not have a paracentesis within 3 months of screening.

7. Protocol specified baseline hematology and kidney function laboratory values

Key

Exclusion Criteria

1. Concurrent participation in another therapeutic clinical study.
2. Symptomatic brain metastases or leptomeningeal involvement.
3. Major surgery within 4 weeks.
4. Clinically significant cardiovascular disease.
5. History of non-pharmacologically induced prolonged QT interval corrected for heart rate interval.
6. Known active infections requiring ongoing treatment (bacterial, fungal, or viral, including human immunodeficiency virus positivity).
7. Gastrointestinal disease or other malabsorption syndromes.
8. Current use or anticipated need for drugs that are known to be strong cytochrome P450 (CYP) 3A inhibitors or inducers.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Repotrectinib (TPX-0005)	repotrectinib (TPX-0005)	Oral repotrectinib (TPX-0005): Cohort 1: Patients with moderate hepatic impairment Cohort 2: Patients with severe hepatic impairment Cohort 3: Patients with normal hepatic function

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve (AUC) of repotrectinib	Within 22 days of first repotrectinib dose	AUC0-t: Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration
Maximum Observed Plasma Concentration (Cmax) of repotrectinib	Within 22 days of first Repotrectinib dose	Cmax: Evaluate the maximum plasma concentration

Secondary Outcome Measures

Name	Time	Method
Evaluate safety and tolerability	28 days after last dose of repotrectinib	To evaluate the safety and tolerability of repotrectinib in patients with moderate and severe hepatic impairment and patients with normal hepatic function following single and multiple dose administration of repotrectinib assessed by CTCAE v5.0

Trial Locations

Locations (2)

Local Institution - 4103; 🇪🇸 Madrid, Spain

Gabrail Cancer Research Center; 🇺🇸 Canton, Ohio, United States