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

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)

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)

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.

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.