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Axatilimab + olaparib is an investigational combination therapy being evaluated for the treatment of metastatic HER2-negative breast cancer in patients with BRCA1/2 or PALB2 mutations. Axatilimab is a humanized monoclonal antibody that targets the colony-stimulating factor 1 receptor (CSF1R), which is expressed on monocytes and macrophages; by inhibiting CSF1R, it aims to deplete or reprogram immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment. Olaparib is an oral poly (ADP-ribose) polymerase (PARP) inhibitor that blocks DNA repair pathways, leading to synthetic lethality in cancer cells with homologous recombination deficiencies (HRD), such as those with BRCA mutations. The combination is being studied by the Dana-Farber Cancer Institute in the Phase Ib AXALAP trial to investigate whether modulating the myeloid compartment of the tumor microenvironment can overcome resistance or enhance the clinical activity of PARP inhibition.
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