A Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Solid Tumors

NCT05071183 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CA127-1025TPX-0005-13
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

A Phase 1b/2 Study of Repotrectinib in Combination with Other Anticancer Therapies for the Treatment of Subjects with KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)

Conditions

KRAS Mutation-Related Tumors; Metastatic Solid Tumor; Advanced Solid Tumor

Keywords

KRAS; KRAS-mutant; Metastatic Solid Tumor; Advanced Solid Tumor; Advanced/metastatic disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities

  Number of participants with first cycle DLTs to determine Mean Tolderable Dose (MTD) and/or RP2D. A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that meets the criteria defined in each subprotocol. The MTD is defined as the highest dose level of repotrectinib given in combination with other anticancer therapy observed to cause a DLT in fewer than 33% of the treated subjects in the first treatment cycle (i.e., Cycle 1).

  From initial dose to end of first cycle of treatment, approximately 28 days

Secondary Outcomes (7)

• Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1.

  From screening to end of treatment approximately 10 months

• Cmax of Repotrectinib

  At Cycle 1 Day 1 and Cycle 1 Day 22

• Tmax of Repotrecitinib

  At Cycle 1 Day 1 and Cycle 1 Day 22

• AUC 0-24 of Repotrecitinib

  At Cycle 1 Day 1 and Cycle 1 Day 22

• Cmax of Trametinib

  At Cycle 1 Day 1 and Cycle 1 Day 22

Study Arms (1)

TPX-0005 + Trametinib

EXPERIMENTAL

TPX-0005 + Trametinib Dose Escalation and Dose Expansion Dose escalation: KRAS G12D mutant advanced solid tumors. Dose expansion: KRAS G12D locally advanced or metastatic NSCLC

Drug: TPX-0005; Drug: Trametinib

Interventions

TPX-0005 DRUG

Oral TPX-0005 capsules

Also known as: repotrectinib

TPX-0005 + Trametinib

Trametinib DRUG

Oral trametinib tablets

Also known as: Mekinist

TPX-0005 + Trametinib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 (or as required by local regulation).
• Histological or cytological confirmation of unresectable or metastatic solid tumor malignancy harboring a KRAS mutation.
• No more than 3 prior standard treatments appropriate for tumor type and stage of disease.
• ECOG performance status ≤ 1.
• Existence of measurable disease (according to Response evaluation criteria in solid tumors \[RECIST v1.1\] criteria).
• Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible.
• Adequate organ function.

You may not qualify if:

• Major surgery within four weeks of the start of treatment.
• Previous other cancer requiring treatment within the previous two years.
• Clinically significant cardiovascular disease.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
• Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A inhibitors or inducers.

Sponsors & Collaborators

• Turning Point Therapeutics, Inc.: lead

Study Sites (6)

Local Institution - 2101

California City, California, 90033, United States

Location

Local Institution - 2109

California City, California, 92663, United States

Location

Local Institution - 2106

Denver, Colorado, 80218, United States

Location

Local Institution - 2108

Nashville, Tennessee, 37203, United States

Location

Local Institution - 2107

Houston, Texas, 77030, United States

Location

Local Institution - 2102

Virginia Beach, Virginia, 22031, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

repotrectinib; trametinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study terminated early by sponsor before initiation of phase 2, so phase 2 outcome measures and endpoint data will not be reported.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: October 8, 2021
• Study Start: September 23, 2021
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: April 2, 2024
• Results First Posted: April 2, 2024

Record last verified: 2024-03

Locations

US (6)