XL888

Our ex vivo senolytic screening platform identifies XL888, an HSP90 inhibitor, that clears p16Ink4a+ cancer-associated fibroblasts in vivo. XL888 administration after establishment of advanced LUAD significantly reduces tumor burden concurrent with the loss of plastic tumor cells. Our study identifies a druggable component of the tumor stroma that fulfills the metabolic requirement of tumor cells to acquire a more aggressive phenotype.

P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2025 --> Nov 2025

These findings suggest local and systemic immune activation by the combination of pembrolizumab and XL888. While clinical activity was modest in treatment-refractory CRC patients, there were notable effects on the tumor immune environment and systemic immune modulation.

A combinatorial computational approach identified the potential anti-cancerous drug among XL888, 5-bromouracil, 5-fluorouracil, and Ganetespib against APC which is often treated as gatekeeper of CRC. This in silico investigation revealed Ganetespib as a potential anti-cancerous drug against APC for CRC therapeutics, which will be an alternative to chemotherapy. In vitro and in vivo studies are needed further to confirm the efficiency and evaluate potency of Ganetespib against the target.

P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2024 --> Mar 2025

Our ex vivo senolytic screening platform identified XL888, a HSP90 inhibitor, that cleared p16 Ink4a + cancer- associated fibroblasts in vivo . XL888 administration after establishment of advanced lung adenocarcinoma significantly reduced tumor burden concurrent with the loss of plastic tumor cells. Our study identified a druggable component of the tumor stroma that fulfills the metabolic requirement of tumor cells to acquire a more aggressive phenotype.

P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute

P1, N=49, Completed, Emory University | Active, not recruiting --> Completed

Combined vemurafenib and cobimetinib plus XL888 had significant toxicity, requiring frequent dose reductions, which may have contributed to the relatively low progression-free survival despite a high tumor response rate. Given overlapping toxicities, caution must be used when combining HSP90 inhibitors with BRAF and MEK inhibitors.

P1, N=21, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

P1, N=21, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2022 --> Dec 2023

P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2022 --> Oct 2023