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

Arm 10_Lung cancer

Arm 10- Perspective cohort

Patients with lung cancer harboring NTRK fusions

Patients with melanoma, non secretory breast and colorectal cancer harboring NTRK fusions.

Arm 10_Lung cancer

Arm 10- Perspective cohort

<p>Inclusion Criteria:</p><ul><li>Locally advanced or metastatic non-secretory breast cancer, lung cancer, melanoma, and colorectal cancer with unknown human neurotrophic tyrosine receptor kinase 1 (NTRK1), NTRK2, or NTRK3 fusion status.</li><li>Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.</li><li>Subjects must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.</li></ul><p>Exclusion Criteria:</p><ul><li>Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (TRK).
Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.</li><li>Symptomatic or unstable brain metastases.
(Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.)
Subjects with primary central nervous system (CNS) tumors are eligible.</li><li>Pregnancy or lactation.</li><li>Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures.</li><li><p>Unstable cardiovascular disease is defined as:</p><ul><li>In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) &gt; 150 mmHg and&#x2F;or diastolic BP &gt; 100 mmHg despite antihypertensive therapy.</li><li>Myocardial infarction within 3 months of screening.</li><li>Stroke within 3 months of screening.</li></ul></li></ul>

<p>Inclusion Criteria:</p><ul><li>Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly-certified laboratories.</li><li>Subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.</li><li><p>Subjects must have at least one measurable lesion as defined by RECIST v1.1.
Subjects with solid tumors without RECIST v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to Cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type.
Subjects with primary CNS tumors should meet the following criteria</p><ol><li>Have received prior treatment including radiation and&#x2F;or chemotherapy, with radiation completed &gt; 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type.</li><li>Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.</li><li>Imaging study performed within 28 days before enrollment.
If on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study.</li><li>Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.</li></ol></li><li>Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) ≥50%</li><li>Tumor tissue before treatment (mandatory).
If neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor.</li><li>Willingness of men and women of reproductive potential to use double effective birth control methods, defined as one used by the subject and another by his&#x2F;her partner, for the duration of treatment and for 1 month following study completion.</li></ul><p>Exclusion Criteria:</p><ul><li>Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (TRK).
Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.</li><li>Symptomatic or unstable brain metastases.
(Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.)
Subjects with primary central nervous system (CNS) tumors are eligible.</li><li>Pregnancy or lactation.</li><li>Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures.</li><li><p>Unstable cardiovascular disease is defined as:</p><ul><li>In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) &gt; 150 mmHg and&#x2F;or diastolic BP &gt; 100 mmHg despite antihypertensive therapy.</li><li>Myocardial infarction within 3 months of screening.</li><li>Stroke within 3 months of screening.</li></ul></li></ul>

NOT_YET_RECRUITING

RECRUITING

NOT_YET_RECRUITING

RECRUITING

2021-09

2021-10

2021-09-06

2021-10-18

2021-09-08

2021-10-25

<p>Availability of this study&#x27;s data will be determined according to Bayer&#x27;s commitment to the EFPIA&#x2F;PhRMA &quot;Principles for responsible clinical trial data sharing&quot;.
This pertains to scope, timepoint and process of data access.</p><p>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.</p><p>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.</p>

<p>Availability of this study&#x27;s data will later be determined according to Bayer&#x27;s commitment to the EFPIA&#x2F;PhRMA &quot;Principles for responsible clinical trial data sharing&quot;.
This pertains to scope, timepoint and process of data access.</p><p>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.</p><p>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.</p>