abemaciclib + osimertinib

abemaciclib + osimertinib is a combination therapy being evaluated for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Abemaciclib, developed by Eli Lilly and marketed as Verzenio, is a selective small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). It functions by preventing the phosphorylation of the retinoblastoma (Rb) protein, which blocks cell cycle progression from the G1 to the S phase, thereby inhibiting tumor cell proliferation. Osimertinib, developed by AstraZeneca and marketed as Tagrisso, is a third-generation irreversible EGFR tyrosine kinase inhibitor (TKI) that targets both sensitizing mutations and the T790M resistance mutation. The University of California, San Diego is sponsoring a Phase II clinical trial (NCT04545710) to investigate whether adding abemaciclib to osimertinib can overcome resistance in patients with metastatic NSCLC who have progressed on osimertinib monotherapy. Preclinical evidence suggests that CDK4/6 inhibition can bypass resistance mechanisms that maintain Rb phosphorylation despite EGFR inhibition.

Brand names

VerzenioTagrisso

Other names

abemaciclib + osimertinib