afatinib + palbociclib

Afatinib + palbociclib is a combination drug repurposing strategy being developed by Collaborations Pharmaceuticals for the treatment of chordoma, a rare and aggressive bone cancer. This therapeutic approach combines two FDA-approved small molecule kinase inhibitors: afatinib, an irreversible pan-ErbB family inhibitor (targeting EGFR, HER2, and HER4), and palbociclib, a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). By simultaneously inhibiting these distinct oncogenic signaling pathways, the combination aims to overcome the limitations of monotherapy in chordoma. Preclinical studies conducted by Collaborations Pharmaceuticals demonstrated significant synergy in vitro (combination index of 0.43) and efficacy in patient-derived xenograft (PDX) mouse models, where the combination effectively halted tumor growth. While both agents are currently in separate Phase 2 trials for chordoma, their combined use remains in the preclinical stage of development.