Larotrectinib(Vitrakvi, BAY2757556)

Data on other treatments

This is an observational study in which patient data from the past of adult people with solid tumors harboring NTRK gene fusion are studied. This study will focus on 5 tumor types which have been at the late stage or have spread to other parts of the body. These 5 tumor types are:

* Non-small-cell-lung cancer
* Colorectal cancer (located in the intestine)
* Thyroid cancer
* Sarcomas (located in the connective tissue like bones or body fat)
* Salivary gland carcinoma

In some people with cancer, the cancer cells have specific changes in their building plans (genes) called NTRK gene fusion. NTRK stands for neurotrophic tyrosine receptor kinase, the specific gene that is changed. Due to this change in the gene, an altered protein known as a TRK fusion protein is made, which can cause cancer cells to grow and survive. While NTRK is the gene, TRK (tropomyosin receptor kinase) is the name of the protein. The specific cancer is therefore also called TRK fusion-positive cancer.

The study drug, larotrectinib works by blocking the altered TRK fusion protein. Larotrectinib is already available in the US, Europe, and in other countries and is approved for doctors to prescribe to patients with TRK fusion cancer.

The main purpose of this study is to learn more about how well larotrectinib works in adults with TRK fusion-positive cancer compared to other treatments. Researchers will compare how long participants who received larotrectninib lived to how long participants who received other treatments lived. To do this, larotrectinib data from past clinical studies will be compared with data on other treatments gathered from different health data sources. The data will cover the time between January 2013 and end of August 2022.

Besides this data collection, no further tests or examinations are planned and no visits are required in this study.

A Study Called VICTORIA to Learn More About How Well Larotrectinib Works in Adults With TRK Fusion-positive Cancer by Comparing Larotrectinib Data From Clinical Studies With Data of Other Treatments From Actual Practice

Comparative Effectiveness Study of Real-world Control of TRK Fusion Positive Cancer With Patients From Larotrectinib (Vitrakvi) Clinical Trials

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

Bayer

Amino Acids

All Drugs and Chemicals

Tyrosine

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

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

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

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

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

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

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.

BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.

Larotrectinib (Vitrakvi, BAY2757556)

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.

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.

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

A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.

Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Sarcoma

Biliary Tract Cancer

Soft Tissue Sarcoma

Pharmaceutical Solutions

Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)

Patients with solid thyroid tumors harboring NTRK fusions (arm closed)

Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)

Patients with solid colorectal tumors harboring NTRK fusions (arm closed)

Patients with solid salivary tumors harboring NTRK fusions (arm closed)

Patients with solid biliary tumors harboring NTRK fusions (arm closed)

Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)

Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions (arm closed)

Patients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)

Patients with melanoma, non secretory breast and colorectal cancer or other tumor types harboring NTRK fusions, except soft tissue sarcoma, salivary gland and thyroid cancer (arm closed)

Patients with all tumor types harboring NTRK fusions, not eligible for the main prospective cohort, including patients with non-measurable disease

Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.

BAY2757556 (Larotrectinib, Vitrakvi)

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

The primary objective of this study is to investigate the efficacy of larotrectinib for the treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor kinase (NTRK) of types 1-3 in children and adults.

Secondary objectives comprise the efficacy and safety of larotrectinib in different NTRK-tumor types.

A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

A Study to Learn How Well the Drug Larotrectinib Works in Adults With Different Solid Cancers With a Change in the Genes Called NTRK Fusion

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by an independent radiology committee (IRC).

Concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with the diagnostic test being evaluated by the Sponsor.

Symptoms and General Pathology

Neoplasm Metastasis

Selitrectinib

Enzyme Inhibitors

A Rolling-6 dose escalation design will be used. The starting dose for participants age \< 12 years will be 25% below the highest dose level cohort divided by 1.73 m\^2 cleared by the Safety Review Committee (SRC) for subjects age 12 years and older.

A 3+3 dose escalation design will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study, enrolling 3 to 6 participants per cohort with a starting dose level of 100 mg twice daily (BID).

Selitrectinib is administered as capsules or liquid formulation.

Selitrectinib (BAY2731954)

This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.

The primary objective is to determine the recommended dose for further study of oral selitrectinib with previously treated neurotrophic tyrosine kinase (NTRK) cancers in 2 patient groups: a) aged 12 years and older and b) younger than 12 years. Secondary objectives of Phase I are to characterize the pharmakokinetic properties of the test drug, its safety and tolerability, and to assess the objective response rate (ORR) of NTRK-tumors.

A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer

A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

Severity is assessed using CTCAE version 4.03

ORR is determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

ORR is determined by the treating investigator using the Response Assessment in Neuro-Oncology (RANO) criteria.

Healthy male participants receive a single dose of 25 mg selitrectinib (Period 1) and 75 mg selitrectinib (Period 2) in fasted state.

Healthy male participants receive a single dose of 50 mg selitrectinib in fasted state (Period 1) and 50 mg selitrectinib in fed state (Period 2).

Healthy male participants receive a single dose of 100 mg selitrectinib (Period 1) and 150 mg selitrectinib (Period 2) in fasted state.

Selitrectinib is administered orally as liquid suspension (20 mg/mL) on Day 1 of each period. Each period lasts 4 days, both periods of each arm are separated by at least 3 days.

The researchers in this study want to gather information in healthy adult male participants about how the human body absorbs, distributes and excretes the drug selitrectinib including the effect of the interaction of food with the study drug on the human body. Selitrectinib is a new drug under development for the treatment of patients with solid tumor caused by a genetic abnormality known as an NTRK gene fusion which cannot be cured by currently available treatment options or has spread to other parts of the body. The drug blocks the action of the NTRK gene fusion and prevents the activation of certain proteins (TRK fusion proteins), which can cause cancer cells to multiply and form a tumor. Researchers also want to find out if the participants have any medical problems during this study.

Participants in this study will receive the study drug twice with at least 6 days in between. The study drug will be taken orally as a liquid before or after meal. Observation will last for up to 8 weeks, and blood samples will be taken from the participants to measure the blood levels of the study drug.

The primary objectives of this study are to investigate the pharmacokinetics and the effect of food on the pharmacokinetics of selitrectinib after a single dose of the drug.

Secondary objective is to assess the safety of selitrectinib after a single dose.

Study in Healthy Adult Male Participants to Gather Information How the Human Body Absorbs, Distributes and Excretes the Study Drug Selitrectinib Including the Effect of the Interaction of Food With the Study Drug on the Human Body

An Open-label, Non-randomized, Phase I Study to Evaluate the Pharmacokinetics of Selitrectinib (BAY 2731954) and Food Effects in Healthy Adult Male Participants

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Selitrectinib expanded access is for minor and adult patients with cancer having a change in a particular gene (NTRK1, NTRK2, or NTRK3 gene fusion). The patients are ineligible for an ongoing selitrectinib clinical trial or have other considerations that prevent access to selitrectinib through an existing clinical trial. Expanded access is intended to treat individual patients with different types of cancers with a NTRK gene fusion, including blood cancers, who have previously received tropomyosin receptor kinase (TRK) inhibitor therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Called VICTORIA to Learn More About How Well Larotrectinib Works in Adults With TRK Fusion-positive Cancer by Comparing Larotrectinib Data From Clinical Studies With Data of Other Treatments From Actual Practice	NCT05192642	Solid Tumors Ha...	Larotrectinib(V... Data on other t...	18 Years -	Bayer
A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer	NCT02122913	Solid Tumors Ha...	Larotrectinib (...	18 Years -	Bayer
A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors	NCT02576431	Solid Tumors Ha...	BAY2757556 (Lar...	18 Years -	Bayer
A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer	NCT03215511	Solid Tumors Ha...	Selitrectinib (...	1 Month -	Bayer
Study in Healthy Adult Male Participants to Gather Information How the Human Body Absorbs, Distributes and Excretes the Study Drug Selitrectinib Including the Effect of the Interaction of Food With the Study Drug on the Human Body	NCT04275960	Solid Tumors Ha...	Selitrectinib (...	18 Years - 45 Years	Bayer
A Study Called VICTORIA to Learn More About How Well Larotrectinib Works in Adults With TRK Fusion-positive Cancer by Comparing Larotrectinib Data From Clinical Studies With Data of Other Treatments From Actual Practice	NCT05192642	Solid Tumors Ha...	Larotrectinib(V... Data on other t...	18 Years -	Bayer
Expanded Access to Provide Selitrectinib for the Treatment of Cancers With a NTRK Gene Fusion	NCT03206931	Solid Tumors Ha...	Selitrectinib (...	1 Month -	Bayer

Spots Global Cancer Trial Database for solid tumors harboring ntrk fusion