A phase 2 study of tarloxotinib in patients with NSCLC harboring EGFR exon 20 insertion or HER2-activating mutations (RAIN)
Description
This is a Phase 2 multicenter, open-label study to evaluate the antitumor effect of tarloxotinib in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) and whose tumor harbors either: 1) an EGFR exon 20 insertion (Cohort A), 2) a HER2-activating mutation (including HER2 exon 20 insertions) (Cohort B), or 3) patients with any solid tumor that harbors NRG1 and ERBB/HERfamily gene fusions (Cohort C).
Status
Accepting new patients
Primary Study Objective(s)
The primary objective of this study is to evaluate the objective response rate of tarloxotinib.
Core eligibility
Note: This is only a partial list of eligibility criteria.
Including patients who meet the following 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)
Excluding patients who meet the following 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
- 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 five 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 percent
- 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