Clinical Research Directory

Inclusion criteria: All parts * Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in tumour tissue or blood prior to screening * At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ function * Age ≥18 years of age, or over the legal age of consent as required by local legislation. * Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial. * Women of childbearing potential who are not surgically sterilized must have a negative serum pregnancy test completed during the Screening period * Further inclusion criteria apply Monotherapy and combination therapy dose escalation and monotherapy dose confirmation part \- Documented disease progression despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage Combination dose confirmation and expansion cohort * Pathologically confirmed diagnosis of adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology. * Locally advanced stage IIIb or metastatic stage IV Non-small cell lung cancer (NSCLC) * Patients must have received both chemotherapy and immunotherapy Exclusion criteria: All parts * Previous anticancer chemotherapy within 3 weeks of the first administration of trial drug. * Previous treatment with RAS, Mitogen-activated protein kinase (MAPK) or Son of sevenless 1 (SOS1) targeting agents * Major surgery performed within 4 weeks prior to start of treatment * Uncontrolled hypertension, congestive heart failure NYHA classification of ≥3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to start of treatment * Left ventricular ejection fraction (LVEF) \<50 % * Congenital long QT prolongation syndrome * Mean resting corrected QT interval (QTcF) \>470 msec * Leptomeningeal carcinomatosis * Presence or history of uncontrolled or symptomatic brain metastases * Known pre-existing interstitial lung disease * Known active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B Deoxyribonucleic acid (DNA)), active hepatitis C infection (defined as presence of Hep C Ribonucleic acid (RNA)) * Active infectious disease * Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug * History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) * Further exclusion criteria apply Combination part \- Hypersensitivity to any of the excipients listed in the current Summary of Product Characteristics (SmPC)/Package insert (PI) of trametinib