Osimertinib Plus Dalpiciclib in Patients With EGFR-mutant, CDK4/6 Pathway Aberrant, Advanced Non-small Cell Lung Cancer Following Acquired Resistance to Third-generation EGFR TKI: a Phase II Trial

Inclusion Criteria: * ECOG performance status 0 to 2 with a minimum life expectancy of 12 weeks * Advanced non-small cell lung cancer with EGFR-sensitive mutation * Confirmed medical history of acquired resistance to third-generation EGFR TKI * Concurrent CDK4/6 pathway gene dysfunctional aberrations * Evaluable or measurable disease as defined by RECIST, Version 1.1 * At least one prior line of systemic chemotherapy * Adequate organ function Exclusion Criteria: * Prior treatment with any CDK4/6 inhibitor * Active uncontrolled/unstable CNS metastases, carcinomatous meningitis, or leptomeningeal disease * Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior platinum therapy related neuropathy. * active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhoea Grade ≥2, malabsorption syndrome or previous significant bowel resection). * Unstable angina pectoris, Congestive heart failure, Acute myocardial infarction, Stroke or transient ischemic attack or other uncontrolled cardiovascular disease currently or within the last 6 months, Mean resting correct QT interval (QTcF) \>470 msec for women and \>450 msec for men at Screening, obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value. * …