A Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Solid Tumors
- Conditions
- KRAS Mutation-Related TumorsAdvanced Solid TumorMetastatic Solid Tumor
- Interventions
- Registration Number
- NCT05071183
- Lead Sponsor
- Turning Point Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TPX-0005 + Trametinib TPX-0005 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 TPX-0005 + Trametinib Trametinib 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
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities From initial dose to end of first cycle of treatment, approximately 28 days 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).
- Secondary Outcome Measures
Name Time Method Tmax of Trametinib At Cycle 1 Day 1 and Cycle 1 Day 22 Tmax is defined is the time to maximum plasma concentration
Tmax of Repotrecitinib At Cycle 1 Day 1 and Cycle 1 Day 22 Tmax is defined is the time to maximum plasma concentration
Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1. From screening to end of treatment approximately 10 months 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.Cmax of Repotrectinib At Cycle 1 Day 1 and Cycle 1 Day 22 Cmax is defined as maximum plasma concentration of the drug.
AUC 0-24 of Repotrecitinib At Cycle 1 Day 1 and Cycle 1 Day 22 Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose.
Cmax of Trametinib At Cycle 1 Day 1 and Cycle 1 Day 22 Cmax is defined as maximum plasma concentration of the drug.
AUC 0-24 of Trametinib At Cycle 1 Day 1 and Cycle 1 Day 22 Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose.
Trial Locations
- Locations (6)
Local Institution - 2107
🇺🇸Houston, Texas, United States
Local Institution - 2102
🇺🇸Virginia Beach, Virginia, United States
Local Institution - 2101
🇺🇸California City, California, United States
Local Institution - 2106
🇺🇸Denver, Colorado, United States
Local Institution - 2109
🇺🇸California City, California, United States
Local Institution - 2108
🇺🇸Nashville, Tennessee, United States