We Partner 4 Research

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

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

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)

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

Arm	Description	Assigned Intervention
Experimental Active	tarloxotinib bromide	Drug: tarloxotinib bromide weekly intravenous infusion Other names: Tarlox tarloxotinib