Clinical trial NCT05071183: A Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Solid Tumors
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: KRAS Mutation-Related Tumors
Metastatic Solid Tumor
Advanced Solid Tumor
Keywords: KRAS
KRAS-mutant
Metastatic Solid Tumor
Advanced Solid Tumor
Advanced/metastatic disease
Lead sponsor: Turning Point Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-08
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: From initial dose to end of first cycle of treatment, approximately 28 days
Secondary outcomes:
measure: Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1.
timeFrame: From screening to end of treatment approximately 10 months
measure: Cmax of Repotrectinib
timeFrame: At Cycle 1 Day 1 and Cycle 1 Day 22
measure: Tmax of Repotrecitinib
timeFrame: At Cycle 1 Day 1 and Cycle 1 Day 22
measure: AUC 0-24 of Repotrecitinib
timeFrame: At Cycle 1 Day 1 and Cycle 1 Day 22
measure: Cmax of Trametinib
timeFrame: At Cycle 1 Day 1 and Cycle 1 Day 22
measure: Tmax of Trametinib
timeFrame: At Cycle 1 Day 1 and Cycle 1 Day 22
measure: AUC 0-24 of Trametinib
timeFrame: At Cycle 1 Day 1 and Cycle 1 Day 22
Other outcomes:
Locations:
city: California City
country: United States
facility: Local Institution - 2101
state: California
city: California City
country: United States
facility: Local Institution - 2109
state: California
city: Denver
country: United States
facility: Local Institution - 2106
state: Colorado
city: Nashville
country: United States
facility: Local Institution - 2108
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 2107
state: Texas
city: Virginia Beach
country: United States
facility: Local Institution - 2102
state: Virginia
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: