Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations

NCT ID: NCT04161391

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-06
• Study Completion Date: 2023-05-22

Brief Summary

A phase 1/2, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel RET/SRC inhibitor TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring RET mutations or alterations. The study consists of three portions: 1) Phase 1 Dose Escalation and Food Effect Sub-study, and 2) Phase 1 dose expansion and 3) Phase 2 efficacy evaluation.

Detailed Description

Phase 1 Dose Escalation and Dose Expansion: To evaluate the overall safety profile, characterize the PK profiles and assess the preliminary efficacy of TPX-0046 in adults subjects with advanced solid tumors harboring oncogenic RET fusions or mutations.

Food Effect Sub-Study: To determine the effect of food on PK of TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring oncogenic RET fusions or mutations.

Phase 2 Efficacy Evaluation: To determine the overall safety and anti-tumor efficacy of TPX-0046 in defined cohorts of subjects with advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations.

Conditions

Non Small Cell Lung Cancer; Medullary Thyroid Cancer; RET Gene Mutation; Metastatic Solid Tumor; Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TPX-0046

The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0046.

The food-effect sub-study determines the effect of food on a dose of TPX-0046 at the RP2D dose level.

The Phase 2 part of the study will determine the safety, tolerability, PK, and preliminary efficacy in specific cohorts.

Phase 2 Cohorts:

• Cohort I (NSCLC + RET fusion, RET TKI Therapy Naive)
• Cohort II (NSCLC + RET fusion, RET TKI Therapy Pre-treated)
• Cohort III (MTC + RET mutation, RET TKI Therapy Naive)
• Cohort IV (MTC + RET mutation, RET TKI Therapy Pre-treated)
• Cohort V (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Naive)
• Cohort VI (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Pre-Treated)

Group Type: EXPERIMENTAL

TPX-0046

Intervention Type: DRUG

Oral TPX-0046 capsules

Interventions

TPX-0046

Oral TPX-0046 capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 (or age ≥ 20 as required by local regulation).

2. Histological or cytological confirmation of advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations, who either have disease progression on, or are intolerant to standard therapy; OR are ineligible for standard therapy or for whom no standard therapy exists; OR are unlikely to tolerate or derive clinical benefit from standard therapy in the opinion of the Investigator OR have declined standard therapy.

3. ECOG performance status ≤ 1.

4. Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).

5. Subjects with asymptomatic primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria.

6. Adequate organ function.

7. Life expectancy ≥ 12 weeks.

Exclusion Criteria

1. Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.

2. Presence or history of any other primary malignancy within 3 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma.

3. Major surgery within four weeks of the start of therapy.

4. Clinically significant cardiovascular disease (either active or within six months before enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of CTCAE version 5.0 grade ≥ 2.

5. Any of the following cardiac criteria:

• Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 470 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval

6. Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).

7. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.

8. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.

9. Subjects with current or anticipated need for drugs that are sensitive CYP2C9 substrates with narrow therapeutic indices.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turning Point Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 2129

La Jolla, California, United States

Local Institution - 2128

Orange, California, United States

Local Institution - 2122

Aurora, Colorado, United States

SCRI - HealthOne Denver

Denver, Colorado, United States

Local Institution - 2126

Washington D.C., District of Columbia, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Local Institution - 2130

Tampa, Florida, United States

Local Institution - 2127

Atlanta, Georgia, United States

University of Chicago Medicine

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Local Institution - 2124

Ann Arbor, Michigan, United States

Local Institution - 2131

Detroit, Michigan, United States

Mayo Clinic - Arizona

Rochester, Minnesota, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Local Institution - 2137

Philadelphia, Pennsylvania, United States

Local Institution - 2120

Houston, Texas, United States

Baylor College of Medicine - Baylor Heart Clinic

Houston, Texas, United States

Local Institution - 2135

Fairfax, Virginia, United States

Local Institution - 2132

Seattle, Washington, United States

Local Institution - 6320

Seoul, , South Korea

Countries

United States; South Korea

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

CA129-1036

Identifier Type: OTHER

Identifier Source: secondary_id

TPX-0046-01

Identifier Type: OTHER

Identifier Source: secondary_id

CA129-1036

Identifier Type: -

Identifier Source: org_study_id