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Label indication VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase ( NTRK ) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. FDA label
Also known as Larotrectinib monotherapy
Larotrectinib · 3 trials · 5 indications
The primary endpoint is the complete pulmonary structural response rate to larotrectinib by modified Nies et al thyroid cancer response criteria.
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 |
|---|---|---|
| Larotrectinib monotherapy with 131I therapy | EXPERIMENTAL | Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose. Patients will receive 131I therapy after 6 months of larotrectinib. Larotrectinib will be continued for 5 days after RAI therapy and then patients will enter a wait and see period off treatment. Patients who experience disease progression at any point while on larotrectinib will proceed to 131I therapy and discontinue larotrectinib. |
| 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 monotherapy | DRUG | Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose. |
| 131I therapy | RADIATION | Patients will receive 131I therapy after 6 months of larotrectinib. |
| Larotrectinib (Vitrakvi, BAY2757556) | DRUG | BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles. |
Inclusion Criteria: 1. Age ≥ 1 year 2. Histologic diagnosis of a differentiated thyroid cancer, s/p thyroidectomy and adequate local therapy (e.g., lymph node dissection as per standard of care) for metastatic disease in the neck in the opinion of the treating investigator 3. Anatomically evaluable...
Larotrectinib is used to treat solid tumors that harbor NTRK gene fusions and differentiated thyroid cancer. It is a biomarker-selected therapy, meaning treatment is directed at tumors carrying an NTRK fusion rather than at a single tumor type. It is also being studied in pediatric cancers and thyroid cancer.
Larotrectinib targets NTRK1, NTRK2, and NTRK3, the genes encoding the TRK family of receptor kinases. It is an inhibitor of these targets, so it works by blocking TRK signaling driven by NTRK gene fusions. This targeted action is why tumors are tested for an NTRK fusion before treatment.
Larotrectinib is developed by Bayer AG, which trades under the ticker BAYRY. Bayer is the company behind the drug's clinical development program across solid tumors harboring NTRK fusions and differentiated thyroid cancer.
Larotrectinib is in Phase 2 development. It is an investigational small molecule and remains in clinical development rather than being presented here as an approved product. Its trial record includes Phase 1 and Phase 2 studies, with one trial currently recruiting and others active or completed.
Larotrectinib has been studied in NCT05783323, a recruiting Phase 2 trial testing whether it enhances radioactive iodine avidity in differentiated thyroid cancer, and NCT02637687, an active Phase 1 study of NTRK-fusion tumors in children. A completed Phase 1 adult safety study, NCT02122913, enrolled 75 participants.
Yes. Larotrectinib is also known as Vitrakvi and by the code name BAY2757556. It is sometimes referred to as larotrectinib monotherapy when used as a single agent. These names all refer to the same NTRK inhibitor developed by Bayer.