This article reports the phase Ia/Ib results of LY3300054 alone and in combination with ramucirumab, abemaciclib, or merestinib results of LY3300054 monotherapy and combination with the TIM-3 inhibitor LY3321367 in microsatellite instability–high tumors will be reported separately.
#Synergy 1.10.0 download trial#
The phase Ia/Ib PACT trial was an open-label, multicenter study of the anti-PD-L1 antibody LY3300054 (Eli Lilly and Company) administered alone or in combination with other agents in patients with advanced refractory solid tumors (NCT02791334). Ramucirumab, an FDA-approved inhibitor of VEGFR 2, has similarly shown favorable antitumor activity and manageable safety profiles when combined with the PD-1 antagonist pembrolizumab ( 11, 12) or the PD-L1 antagonist durvalumab ( 13) in patients with previously treated advanced gastrointestinal cancers, NSCLC, and urothelial carcinoma. In addition, bevacizumab in combination with atezolizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib as a first-line treatment for hepatocellular carcinoma. Combining VEGF-targeting therapies with PD-1/PD-L1 inhibitors has shown synergy and positive outcomes in phase I to III studies ( 7), notably those involving bevacizumab, an anti-VEGF antibody now approved for use in combination with the PD-L1 inhibitor atezolizumab and chemotherapy for the first-line treatment of nonsquamous non–small cell lung cancer (NSCLC). Agents targeting VEGF or its receptors can normalize tumor vasculature and increase T-cell infiltration, but also promote dendritic cell maturation and suppress immunosuppressive immune cells such as myeloid-derived suppressor cells and regulatory T cells ( 7–9).
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