an open-label study of encorafenib + binimetinib in patients with brafv600-mutant non-small cell lung cancer

Conditions: Non-small Cell Lung Cancer

Summary: this is an open-label, multicenter, non-randomized, phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with brafv600e-mutant metastatic non-small cell lung cancer (nsclc). patients who are either treatment-naïve, or who have received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-programmed cell death protein 1 (pd-1)/programmed cell death protein ligand 1 (pd-l1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.


Eligibility criteria:
key inclusion criteria: * histologically confirmed diagnosis of non-small cell lung cancer (nsclc) that is currently stage iv. * presence of a brafv600e mutation in lung cancer tissue as determined by a local laboratory assay or the presence of other brafv600 mutations other than v600e (i.e. k or d) will be considered * patients who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), or who have received 1) first-line platinum-based chemotherapy or 2) first-line treatment with an anti-programmed cell death protein 1 (pd-1)/ programmed cell death protein ligand 1(pd-l1) inhibitor given alone or in combination with platinum-based chemotherapy. * presence of measurable disease based on response evaluation criteria in solid tumors version 1.1 (recist v1.1). * eastern cooperation oncology group (ecog) performance status of 0 or 1. * adequate bone marrow function characterized by the following at screening: * absolute neutrophil count (anc) ≥ 1.5 × 10⁹/l; * platelets ≥ 100 × 10⁹/l; * hemoglobin ≥ 8.5 g/dl (with or without blood transfusions). * adequate hepatic and renal function characterized by the following at screening: * total bilirubin ≤ 1.5 × upper limit of normal (uln) * alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 2.5 × uln, or ≤ 5 × uln in presence of liver metastases; serum creatinine ≤ 1.5 × uln; or calculated creatinine clearance ≥ 50 ml/min by cockcroft-gault formula; or estimated glomerular filtration rate \> 50 ml/min/1.73m². key exclusion criteria: * patients who have documentation of any of the following: * epidermal growth factor receptor (egfr) mutation * anaplastic lymphoma kinase (alk) fusion oncogene or * ros1 rearrangement * patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting. * previous treatment with any braf inhibitor (e.g., dabrafenib, vemurafenib, xl281/bms-908662, etc.), or any mitogen-activated protein kinase (mek) inhibitor (e.g., trametinib, cobimetinib, selumetinib, rdea119, etc.) prior to screening and enrollment. * impaired cardiovascular function or clinically significant cardiovascular diseases * history of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment. examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli. * history or current evidence of retinal vein occlusion (rvo) or current risk factors for rvo (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease. * concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phospho)kinase (ck) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). * patients with symptomatic brain metastasis, leptomeningeal disease or other active central nervous system (cns) metastases are not eligible.

Keywords: lung cancer cancer non-small cell lung cancer non small cell lung cancer nsclc encorafenib binimetinib phase 2 open label braf mutation braf v600e array stage iv nsclc metastatic nsclc pdl1 pd-li immunotherapy first line platinum based chemotherapy braf inhibitor v600