Amino Acids

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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

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

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)

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.

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

Recurrence

Disease Attributes

Bayer Clinical Trials Contact

Researchers want to learn more about the use of larotrectinib as a real-world treatment for tropomyosin receptor kinase fusion cancer, also called TRK fusion cancer.

In people with TRK fusion cancer, a gene called neurotrophic TRK, (NTRK) joins or "fuses" with another gene. This creates a protein known as a fusion protein, which can cause cancer cells to grow. The study treatment, larotrectinib, is already available for doctors to prescribe to patients with TRK fusion cancer. Larotrectinib works by blocking TRK genes in cancer cells which helps stop the cancer from growing.

In this study, the researchers want to learn more about the safety and effectiveness of larotrectinib in adults and children with advanced or recurrent TRK fusion cancer. This means that their cancer has spread from where it started to other areas of the body, or the cancer has come back after a period of time. To answer this question, the researchers will collect information from patients who are taking larotrectinib as prescribed by their doctors. The researchers will learn what adverse events the patients are having. An adverse event is any medical problem that a patient has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

The study will include patients of all ages with TRK fusion cancer.

In this study, there will be no required tests or visits to a study site. Instead, the researchers will collect information from:

* the patients' medical records
* interviews with the patients or their parents or guardians
* the patients' visits to their doctor as part of their usual care The researchers will collect information about the adults for up to about 2 years and about the children for up to about 8 years.

NTRK Gene Fusion - Positive Advanced or Recurrent Solid Tumors, a Rare Cancer Caused by Specific Changes in the Genes

Special Drug Use Investigation for Larotrectinib

Including but not limited to: age, NTRK gene, NTRK gene partner, prior therapy (type, number of lines of therapy), other.

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 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
NTRK Gene Fusion - Positive Advanced or Recurrent Solid Tumors, a Rare Cancer Caused by Specific Changes in the Genes	NCT04945330	Advanced or Rec...	Larotrectinib (...	-	Bayer

Spots Global Cancer Trial Database for larotrectinib (vitrakvi, bay2757556)