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

Sponsor

Turning Point Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05071183

Collaborator

(none)

Enrollment

Locations

Arm

27.3

Anticipated Duration (Months)

12.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
KRAS Mutation-Related Tumors Metastatic Solid Tumor Advanced Solid Tumor	Drug: TPX-0005 Drug: Trametinib	Phase 1/Phase 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 23, 2021

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TPX-0005 + 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	Drug: TPX-0005 Oral TPX-0005 capsules Other Names: repotrectinib Drug: Trametinib Oral trametinib tablets Other Names: Mekinist

Arm

Intervention/Treatment

Experimental: TPX-0005 + 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

Drug: TPX-0005

Oral TPX-0005 capsules

Other Names:

repotrectinib

Drug: Trametinib

Oral trametinib tablets

Other Names:

Mekinist

Outcome Measures

Primary Outcome Measures

Evaluate Safety and Tolerability [Three years]
Evaluate the safety and tolerability of repotrectinib in combination with trametinib with treatment-related adverse events as assessed by CTCAE v5.0
Define the Recommended Phase 2 Dose (RP2D) [Approximately 22 months]
Define the objective response rate (ORR) [Two to three years after first dose of Repotrectinib in combination with other anticancer therapies]

Secondary Outcome Measures

Cmax (maximum plasma concentration) of repotrectinib in combination with trametinib [Up to 24 hours post-dose]
Evaluate the maximum plasma concentration of repotrectinib in combination with trametinib
AUC (area under plasma concentration time curve) of repotrectinib in combination with trametinib [Up to 24 hours post-dose]
Determine the AUC of repotrectinib in combination with trametinib
Determine the preliminary efficacy of repotrectinib in combination with trametinib measured by ORR as assessed per RECIST v1.1 [Approximately three years]
Clinical benefit rate (CBR) [Approximately three years]
Progression free survival (PFS) [Approximately three years]
Duration of response (DOR) [Approximately three years]
Time to response (TTR) [Approximately three years]
Overall survival (OS) [Approximately three years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Hoag Memorial Hospital	Newport Beach	California	United States	92663
3	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
4	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee	United States	37203
5	MD Anderson Cancer Center	Houston	Texas	United States	77030
6	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031