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Also known as Larotrectinib (Vitrakvi, BAY2757556)
Larotrectinib · 2 trials · 1 indication
DLT: Dose-limiting toxicity. NCI-CTCAE: National Cancer Institute-Common Terminology Criteria for Adverse Events.
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) as determined by an independent radiology review committee (IRRC) based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, Response Assessment in Neuro Oncology (RANO) or International Neuroblastoma Response Criteria (INRC) as appropriate to tumor type who express NTRK gene fusions.
The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.
| Arm | Type | Description |
|---|---|---|
| Phase 1 dose escalation | EXPERIMENTAL | Patients will receive the different levels of dose on Day 1 (BID in accordance with the cohort assignment). Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. (arm closed) |
| Phase 1 dose expansion | EXPERIMENTAL | Patients who are enrolled in the expansion cohort, following the formal dose escalation phase of the study. Distinct from the Phase 1 dose escalation cohort, the Phase 1 expansion cohort will enroll pediatric patients with advanced solid or primary CNS tumors with a documented NTRK gene fusion, or in the case of IFS, CMN or SBC with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by NGS. This expansion cohort will follow the same schedule of assessments as the dose escalation cohorts. (arm closed) |
| Phase 2: Patients with tumors bearing NTRK fusions (IFS)_Cohort 1 | EXPERIMENTAL | Patients will receive larotrectinib dose on Day 1 (BID in accordance with the cohort assignment) at the recommended Phase 2 dose as determined in the Phase 1 portion of this study. Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. (arm closed) |
| Phase 2: Other extra-cranial solid tumors_Cohort 2 | EXPERIMENTAL | Patients will receive larotrectinib dose on Day 1 (BID in accordance with the cohort assignment) at the recommended Phase 2 dose as determined in the Phase 1 portion of this study. Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. (arm closed) |
| Phase 2: Primary CNS tumors_Cohort 3 | EXPERIMENTAL | Patients will receive larotrectinib dose on Day 1 (BID in accordance with the cohort assignment) at the recommended Phase 2 dose as determined in the Phase 1 portion of this study. Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. |
| Phase 2: Bone health assessment_sub-cohort | EXPERIMENTAL | Patients will receive larotrectinib dose on Day 1 (BID in accordance with the cohort assignment) at the recommended Phase 2 dose as determined in the Phase 1 portion of this study. Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. Patients in this group will undergo bone health assessments in addition to all other efficacy and safety assessments. |
| Tumor patients_Dose 1 | EXPERIMENTAL | Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort). |
| Tumor patients_Dose 2 | EXPERIMENTAL | Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort). |
| Tumor patients_Dose 3 | EXPERIMENTAL | Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort). |
| Tumor patients_Dose 4 | EXPERIMENTAL | Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort). |
| Tumor patients_Dose 5 | EXPERIMENTAL | Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort). |
| Tumor patients_Dose 6 | EXPERIMENTAL | Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort). |
| Tumor patients_Expansion | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| Larotrectinib (Vitrakvi, BAY2757556) | DRUG | BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. |
Inclusion Criteria: * Phase 1 (Closed): * Dose escalation: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curati...
Larotrectinib is an investigational small molecule being developed for the treatment of solid tumors harboring NTRK fusion. It is a kinase inhibitor, and it is currently in Phase 1 clinical development for this indication.
Larotrectinib targets kinases, as it belongs to the -tinib class of kinase inhibitors. It is being studied in patients with solid tumors that harbor NTRK gene fusions, which are genetic alterations that can drive cancer growth.
Larotrectinib is being developed by Bayer AG, a company traded under the ticker BAYRY. The drug is also known as Vitrakvi and BAY2757556.
Larotrectinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. It is being studied in clinical trials for solid tumors harboring NTRK fusion.
Larotrectinib has been studied in two clinical trials. NCT02122913 is a completed Phase 1 study in adults with solid tumors harboring NTRK fusion. NCT02637687 is an active Phase 1 study in children with NTRK-fusion tumors, with 154 participants enrolled.
Yes, Larotrectinib is also known as Vitrakvi and BAY2757556. These names refer to the same investigational drug being developed by Bayer AG for solid tumors harboring NTRK fusion.