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

RAIN-701

Open-label, Phase 2, single treatment arm, 3 cohorts

2019-03-13

2021-04-09

2021-04-23

Terminated

Early phase I

41

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 41, 'type': 'ACTUAL'}}

2023-06-28