Study of Tarloxotinib in Pts With NSCLC (EGFR Exon 20 Insertion, HER2-activating Mutations) & Other Solid Tumors With NRG1/ERBB Gene Fusions
Condition: NSCLC, Stage IV; NSCLC Stage IIIB; NSCLC, Stage IIIC; NSCLC, Recurrent; EGFR Exon 20 Insertion Mutation; HER2-activating Mutation; ERBB Fusion; NRG1 Fusion
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: tarloxotinib bromide
Intervention description: weekly intravenous infusion
Intervention MeSH terms: Bromides
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        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