This is an open-label, single-arm, multicenter phase II trial in patients with stage IV EGFR T790M, EGFR exon 20 and other uncommon, HER2, or BRAF-mutated; ALK, ROS1, or RET-rearranged NSCLC.

NCT01922583

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: AUY922

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

G469A, D594G). --- G469A ---

The goal of this trial is to test the safety and efficacy of an innovative combination aimed to more profoundly inhibit ERK signaling in tumors.

NCT03843775

Conditions

1. Advanced BRAF Mutant Cancers

Interventions

1. Drug: Binimetinib
2. Drug: Encorafenib

- Patient's tumor must harbor an activating BRAF mutation (listed in Table 4 or approved by the study Principal Investigator) or a fusion involving the kinase domain of BRAF - Mechanistically validated activating non-V600 BRAF mutants - P367L/S - G464V/E - G469A/V/R - L485W - N486_A489delinsK - N486_P490del - E586K - L597Q/V/S - T599TT/TS - T599I/K - V600_K601delinsE - K601E/N/T - K601_S602delinsNT - BRAF kinase duplication - Fusions involving BRAF kinase domain - Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 - Adequate bone marrow, organ function and laboratory parameters: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Hemoglobin (Hgb) ≥ 8 g/dL with or without transfusions - Platelets (PLT) ≥ 75 x 109/L without transfusions - AST and/or ALT ≤ 2.5 × upper limit of normal (ULN); patient with liver metastases ≤ 5 ×ULN - Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL (Note: Patients who have a total bilirubin level > 1.5 x ULN will be allowed if their indirect bilirubin level is ≤ 1.5 x ULN) - Serum Creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50 mL/min at screening - Adequate cardiac function: - left ventricular ejection fraction (LVEF) ≥ 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram - QTc interval ≤ 480 ms (preferably the mean from triplicate ECGs) - Able to take oral medications - Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up) - Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through 30 days after the last dose of study drug/treatmentif of childbearing potential (Note: Permitted contraception methods listed in Section 9.3 should be communicated to the patients and their understanding confirmed. --- P367L --- --- G464V --- --- G469A ---