Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer

Inclusion Criteria: * Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation * Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 * Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI * Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) * Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months * Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: * Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification * Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) * Known preexisting interstitial lung disease or pneumonitis * Concurrent use of QT-prolonging medication * Uncontrolled diabetes (HA1C \> 10%) despite optional therapy * Cardiac abnormalities: * Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) \>450 ms * Inability to measure QT interval on ECG * Personal or family history of long QT syndrome * Implantable pacemaker or implantable cardioverter defibrillator * Resting bradycardia \< 55 beats/min * Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment * Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) * Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment * Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients