study of tarloxotinib in pts with nsclc (egfr exon 20 insertion, her2-activating mutations) & other solid tumors with nrg1/erbb gene fusions

Conditions: NSCLC, Stage IV; NSCLC Stage IIIB; NSCLC, Stage IIIC; NSCLC, Recurrent; EGFR Exon 20 Insertion Mutation; HER2-activating Mutation; ERBB Fusion; NRG1 Fusion

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