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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Solid Tumor; Locally Advanced Solid Tumor
• Intervention / Treatment: Drug: repotrectinib (TPX-0005)

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 Type: Interventional
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain the NCT# and Site #.

Study Locations

• Spain
  • Madrid, Spain, 28033
    • Local Institution - 4103
• United States
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Research Center

Participation Criteria

Eligibility Criteria

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

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: 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	Drug: repotrectinib (TPX-0005); Oral repotrectinib (TPX-0005); Other Names: repotrectinib; Oral TPX-0005 capsules

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate safety and tolerability	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	28 days after last dose of repotrectinib

Collaborators and Investigators

• Sponsor: Turning Point Therapeutics, Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2022
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CA127-1026 (Other Identifier: BMS Protocol ID); TPX-0005-15 (Other Identifier: Turning Point Therapeutics Protocol ID)

Drug and device information, study documents

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