Phase 2 Study of Tarloxotinib in Patients With NSCLC Harboring EGFR Exon 20 Insertion or HER2-activating Mutations

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

- Progression of disease on or after a platinum-based chemotherapy regimen

- EGFR exon 20 insertion mutation (Cohort A) or HER2 activating mutation (Cohort B)

- 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

- Previously received anti EGFR or anti HER2 tyrosine kinase inhibitors

- 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