GB1275 + nab-paclitaxel + gemcitabine

GB1275 + nab-paclitaxel + gemcitabine is an investigational combination therapy for solid tumors, notably for pancreatic ductal adenocarcinoma (PDAC). It consists of GB1275, an oral small-molecule allosteric modulator and agonist of CD11b, nab-paclitaxel (a nanoparticle formulation of paclitaxel), and gemcitabine (a nucleoside analog chemotherapy). GB1275 activates CD11b on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), reducing their migration into the tumor microenvironment and repolarizing TAMs toward pro-inflammatory M1 phenotypes, thereby enhancing anti-tumor immune response[1][2][3][5]. In preclinical and early clinical studies, GB1275’s allosteric activation of CD11b impairs myeloid cell extravasation, increases antigen presentation, and potentiates T cell recruitment via STING and STAT1 pathway activation[1][3][5]. Nab-paclitaxel stabilizes microtubules, inhibiting cell division, while gemcitabine is phosphorylated within malignant cells, resulting in masked DNA chain termination and apoptosis[4]. The triplet regimen aims to reduce immunosuppressive myeloid infiltration, reprogram the tumor immune microenvironment, and directly kill tumor cells, with promising preclinical efficacy in PDAC models over standard chemotherapy or single agents[1].

Brand names

AbraxaneGemzar

Other names

leukadherin-1 salt (for GB1275)