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

Turning Point Therapeutics

Status and phase: Terminated; Phase 2; Phase 1

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

Treatments: Drug: Trametinib; Drug: TPX-0005

Study type: Interventional

Funder types: Industry

Identifiers

NCT05071183

CA127-1025 (Other Identifier)

TPX-0005-13

Details and patient eligibility

About

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)

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

TPX-0005 + Trametinib

Experimental group

Description:

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

Treatment:

Drug: TPX-0005

Drug: Trametinib