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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
     

Accepting new patients

 

Learn more at

clinicaltrials.gov