A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer

Bayer

Status and phase: Completed; Phase 1

Conditions: Solid Tumors Harboring NTRK Fusion

Treatments: Drug: Larotrectinib (Vitrakvi, BAY2757556)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02122913

LOXO-TRK-14001 (Other Identifier)

20288

Details and patient eligibility

About

This research study is done to test the safety of the drug larotrectinib in adult cancer patients. The drug may be used to treat cancer with a change in a particular gene (NTRK1, NTRK2 or NTRK3), because it blocks the action of these genes in cancer cells. The study also investigates how the drug is absorbed and processed in the human body. This is the first study to test larotrectinib in humans with cancer, for whom no other effective therapy exists.

Full description

The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in subjects with advanced solid tumors will be followed by an expansion phase in subjects with solid tumors having a NTRK fusion.

The objectives of the study are to determine the safety, pharmacokinetic profile, recommended dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists
• Proof of a malignancy harboring a NTRK fusion
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of at least 3 months
• Adequate hematologic, hepatic, and renal function

Exclusion criteria

• Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible
• Clinically significant active cardiovascular disease or history of myocardial infarction
• Active uncontrolled systemic bacterial, viral, or fungal infection
• Current treatment with a strong CYP3A4 inhibitor or inducer
• Pregnancy or lactation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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75 participants in 7 patient groups

Tumor patients_Dose 1

Experimental group

Description:

Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 2

Experimental group

Description:

Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 3

Experimental group

Description:

Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 4

Experimental group

Description:

Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 5

Experimental group

Description:

Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Dose 6

Experimental group

Description:

Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)

Tumor patients_Expansion

Experimental group

Description:

Adults patients with solid tumors and neurotrophic tyrosine kinase (NTRK) genes or proteins of types 1 - 3 (dose expansion cohort). Patients receive either the recommended or maximum tolerated dose of BAY2757556 as determined in the dose escalation part.

Treatment:

Drug: Larotrectinib (Vitrakvi, BAY2757556)