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

Bayer

Pharmaceutical Solutions

Larotrectinib will be administered orally as capsule or liquid solution as specified by the treating physician.

Larotrectinib expanded access is for patients with cancer with a NTRK1, NTRK2, or NTRK3 gene fusion, who are ineligible for an ongoing larotrectinib clinical trial or have other considerations that prevent access to larotrectinib through an existing clinical trial. Gene fusion occurs when a gene is made by joining parts of two different genes. NTRK gene fusion can lead to the development of solid tumors in a variety of tissue types. The study drug larotrectinib blocks the action of the NTRK gene fusion.

Expanded access is intended to treat individual patients with different types of cancers with a NTRK gene fusion who are unresponsive to current standard treatment for their condition and also are unable to participate in ongoing clinical trials.

Expanded Access to Provide Larotrectinib for the Treatment of Cancers With a NTRK Gene Fusion

Expanded Access to Provide Larotrectinib (LOXO-101) for the Treatment of Cancers With a NTRK Gene Fusion

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

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.

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Pediatric patients with IFS harboring an NTRK gene fusion who have been enrolled in the SCOUT study.

Pediatric patients with IFS harboring an NTRK gene fusion in the eligible external cohort(s).

Pediatric patients with IFS harboring an NTRK gene fusion.

Standard of care for the patients from the eligible external cohorts.

Standard of Care

This is an observational study in which data from the past of children and young people with a specific cancer, called NTRK gene fusion positive infantile fibrosarcoma (IFS) is studied.

IFS is a rare type of childhood cancer that commonly affects legs and arms. IFS cancers typically have specific changes in their building plans (genes) called NTRK gene fusion. NTRK stands for the specific gene that has been altered, the neurotrophic tyrosine kinase (NTRK) gene.

This change to the building plan leads to the creation of an altered protein known as a TRK fusion protein, which can cause cancer cells to grow and to survive. The specific cancer is therefore also called TRK (tropomyosin receptor kinase) fusion-positive IFS.

The study drug, larotrectinib (also called BAY2757556) works by blocking the altered TRK fusion protein. Larotrectinib is already available in Europe and in many other countries and is approved for doctors to prescribe to patients with NTRK gene fusion cancer which has spread to nearby tissues and/or lymph nodes or to other parts of the body.

In France, HAS (the French authority in charge of evaluating health products and technologies) gave a positive opinion for the reimbursement of larotrectinib but only in the pediatric patients with IFS or another STS harboring a NTRK gene fusion, which is locally advanced or metastatic, and refractory or in relapse mainly due to the lack of comparative evidence.

The main purpose of this study is to collect more data to learn how well larotrectinib works compared with current standard of care chemotherapy in people up to 21 years of age with NTRK gene fusion positive IFS that has spread to nearby tissues and/or lymph nodes (locally advanced) or other parts of the body (metastatic).

To see how well larotrectinib works, researchers will make a comparison between

* how long larotrectinib works well and
* how long the standard of care works well.

Working well means that the treatments can prevent the following from happening:

* need for a new treatment for the cancer
* need for radiation therapy for the cancer
* need for surgery to treat the cancer, but which causes major damage to body parts
* death.

In addition to the above, data about medical problems related to the treatments in both groups and that may have required to stop the treatment will be compared.

The data for the comparison will come from

* an ongoing international study called SCOUT which was started in December 2015 (larotrectinib group)
* international databases (standard of care chemotherapy group). Data will be from the year 2000 up to the present.

There will be no required visits with a study doctor or required tests in this study.

A Study Called EPI VITRAKVI to Compare Treatment Results in Patients With Infantile Fibrosarcoma (IFS), a Type of Connective Soft Tissue Cancer, Who Received a Treatment Called Larotrectinib From a Study Called SCOUT With Patient Data From an External Database

A Comparison of Clinical Outcomes in Infantile Fibrosarcoma (IFS) Patients Treated With Larotrectinib in the Phase I/II SCOUT Study Versus (an) External Historical Cohort(s)

Defined as the time (months) from the start of treatment to the date of the following events, whichever comes first: subsequent systemic treatment, radiation therapy, mutilating surgery or death due to any cause.

Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the start date of a post-treatment systemic anti-cancer therapy, if any.

Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the date of a post-treatment mutilating surgery including limb amputation, if any.

Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the start date of a post-treatment radiation therapy, if any.

Calculated from the start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s) to the date of a post-treatment complete surgical resection (excluding amputation), if any.

Start date of larotrectinib treatment for the SCOUT study and start date of chemotherapy (first line) for the external historical control cohort(s), Date of death due to any cause, if applicable, or, Last date of patient follow-up for patients alive and lost to follow-up, if applicable.

Larotrectinib treatment for the SCOUT study and chemotherapy (first line) for the external historical control cohort(s).

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.

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 to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer	NCT02122913	Solid Tumors Ha...	Larotrectinib (...	18 Years -	Bayer
Expanded Access to Provide Larotrectinib for the Treatment of Cancers With a NTRK Gene Fusion	NCT03025360	Tumors Harborin...	Larotrectinib (...	-	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 Called EPI VITRAKVI to Compare Treatment Results in Patients With Infantile Fibrosarcoma (IFS), a Type of Connective Soft Tissue Cancer, Who Received a Treatment Called Larotrectinib From a Study Called SCOUT With Patient Data From an External Database	NCT05236257	Locally Advance... Infantile Fibro...	Larotrectinib (... Standard of Car...	- 21 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
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 fusion positive