Study of Tarloxotinib in Pts With NSCLC (EGFR Exon 20 Insertion, HER2-activating Mutations) & Other Solid Tumors With NRG1/ERBB Gene Fusions

Study Overview
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Brief Summary
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Open-label, Phase 2, single treatment arm, 3 cohorts

Official Title
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Phase 2 Study - Evaluate the Clinical Activity of Tarloxotinib in Patients With Non-Small Cell Lung Cancer That Harbors an EGFR Exon 20 Insertion or HER2-Activating Mutation and Other Advanced Solid Tumors With NRG1/ERBB Family Gene Fusions

Conditions
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NSCLC, Stage IV, NSCLC Stage IIIB, NSCLC, Stage IIIC, NSCLC, Recurrent, EGFR Exon 20 Insertion Mutation, HER2-activating Mutation, ERBB Fusion, NRG1 Fusion

Intervention / Treatment
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* Drug: tarloxotinib bromide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically and/or cytologically confirmed primary diagnosis of NSCLC, Stage IV, Stage IIIB or IIIC not amenable to definitive curative intent therapy, or recurrent disease after prior diagnosis of Stage I-III disease. Cohort C locally advanced or metastatic solid tumor. Progression of disease on or after a platinum-based chemotherapy regimen (Cohorts A and B) or after standard of care (Cohort C) EGFR exon 20 insertion mutation (Cohort A) or HER2 activating mutation (Cohort B) or NRG1 or ERBB family gene fusions (Cohort C) Measurable disease according to RECIST v.1.1 ECOG performance status of 0 or 1 Serum creatinine ≤ 1.5 x ULN (or calculated creatinine clearance ≥ 60 mL/min using Cockcroft Gault equation) Total bilirubin: ≤ 1.5 x ULN or ≤ 3 x ULN in the presence of liver metastases Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN, in the presence of liver metastases Absolute neutrophil count (ANC) ≥ 1,500 cells/μL Hemoglobin ≥ 9 g/dL or 5.6 mmol/L Platelet count ≥ 100,000/μL No evidence of second or third degree atrioventricular block No clinically significant arrhythmia (i.e.; pauses of > 4 seconds, VT of any duration, SVT > 4 beats/minute) QRS interval ≤ 110 ms QTcF interval of < 450 ms PR interval ≤ 200 ms Adequate pretreatment tumor sample (125 µm of FFPE block or at least 8 prepared slides) Key Exclusion Criteria: Another known activating oncogene driver mutation (Cohorts A and B Only) Previously received anti EGFR or anti HER2 tyrosine kinase inhibitors (Cohorts A and B Only) Previously received anti EGFR or anti HER2 monoclonal antibodies or EGFR or HER2 antibody drug conjugates Investigational therapy administered within the 28 days or 5 half lives Chemotherapy or radiation within 14 days prior to Cycle 1 Day 1 Immunotherapy within 21 days Clinically active or symptomatic interstitial lung disease (ILD) or interstitial pneumonitis, or a history of clinically significant ILD or radiation pneumonitis Untreated and/or symptomatic CNS malignancies (primary or metastatic); Receiving medication that prolongs QT interval, with a risk of causing Torsade de Pointes (TdP) Personal or familial history of Long QT Syndrome NYHA class III or IV or LVEF < 55% Myocardial infarction, severe or unstable angina within 6 months History of TdP, ventricular arrhythmia Significant thrombotic or embolic events within 3 months Uncontrolled or severe cardiovascular disease Concurrent malignancy expected to require treatment within 2 years or interfere with study outcomes History of severe allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition as tarloxotinib Known HIV infection or active Hepatitis B or C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>tarloxotinib bromide | Drug: tarloxotinib bromide<br>* weekly intravenous infusion<br>* Other names: tarloxotinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | The primary objective of this study is to evaluate the objective response rate (ORR) of tarloxotinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for tumors assessed by CT or MRI: Complete Response (CR) - Disappearance of all target lesions and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm. Partial Response (PR) - ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline. The overall response rate in each cohort will be estimated as the number of subjects with a confirmed objective response (CR or PR) divided by the number of enrolled subjects in each respective cohort. | Through study completion, an average of 10 months. |