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

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