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

Advanced Solid Tumor Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05071183
• Other study ID #: CA127-1025
• Secondary ID: CA127-1025TPX-00
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 23, 2021
• Est. completion date: March 1, 2023

Study information

• Verified date: March 2024
• Source: Turning Point Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

Phase 1 Dose Escalation: To evaluate tolerability of repotrectinib at increasing dose levels in combination with other anticancer therapies for the treatment of subjects with locally advanced or metastatic KRAS-mutant solid tumors

Phase 2 Efficacy Evaluation: Investigate the anti-tumor efficacy and safety of repotrectinib in combination with other anticancer therapies for the treatment of patients with locally advanced or metastatic KRAS-mutant solid tumors.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• KRAS Mutation-Related Tumors
• Metastatic Solid Tumor
• Neoplasms

Intervention

Drug:
• TPX-0005
Oral TPX-0005 capsules
• Trametinib
Oral trametinib tablets

Locations

Country	Name	City	State
United States	Local Institution - 2101	California City	California
United States	Local Institution - 2109	California City	California
United States	Local Institution - 2106	Denver	Colorado
United States	Local Institution - 2107	Houston	Texas
United States	Local Institution - 2108	Nashville	Tennessee
United States	Local Institution - 2102	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Turning Point Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1.	The ORR will be defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A confirmed response is a response that persists on a repeat imaging performed at least 4 weeks after initial documentation of response. Participants with a confirmed objective response (CR or PR) will be referred to as responders.; Radiographic confirmation of objective tumor response (CR or PR) or disease progression will be based on RECIST v1.1. The ORR will be reported as the percentage of responders by RECIST v1.1 along with the corresponding two-sided 95% Clopper-Pearson exact CI.; Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = >=30% decrease in the sum diameters of target lesions.	From screening to end of treatment approximately 10 months
Secondary	Cmax of Repotrectinib	Cmax is defined as maximum plasma concentration of the drug.	At Cycle 1 Day 1 and Cycle 1 Day 22
Secondary	Tmax of Repotrecitinib	Tmax is defined is the time to maximum plasma concentration	At Cycle 1 Day 1 and Cycle 1 Day 22
Secondary	AUC 0-24 of Repotrecitinib	Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose.	At Cycle 1 Day 1 and Cycle 1 Day 22
Secondary	Cmax of Trametinib	Cmax is defined as maximum plasma concentration of the drug.	At Cycle 1 Day 1 and Cycle 1 Day 22
Secondary	Tmax of Trametinib	Tmax is defined is the time to maximum plasma concentration	At Cycle 1 Day 1 and Cycle 1 Day 22
Secondary	AUC 0-24 of Trametinib	Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose.	At Cycle 1 Day 1 and Cycle 1 Day 22

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting