Curis, Inc. and Debiopharm Group™ (Debiopharm) have announced the start of an open-label, multicenter Phase I dose-finding study of Debio 0932, a heat shock protein 90 (HSP90) inhibitor in combination with everolimus (Afinitor®), an inhibitor of mammalian target of rapamycin (mTOR) in patients with advanced or metastatic renal cell carcinoma (RCC), who have been previously treated with a VEGF-directed tyrosine kinase inhibitor.
This dose escalation study is designed to determine the safety and maximum tolerated dose of Debio 0932 in combination with everolimus, in previously treated patients with advanced/metastatic RCC.
The pharmacokinetic profiles and any potential drug-drug interactions between the two agents will also be assessed. The trial also includes an expansion cohort of 25 patients with metastatic clear cell RCC.
While approved monotherapy treatments for RCC, including mTOR inhibitors are active, improved therapies are needed to enhance the depth and duration of response. Several mTOR signaling pathway components such as mTOR, AKT and LKB1 are HSP90 client proteins. Mechanistic data suggest the potential for improved efficacy through dual mTOR and HSP90 inhibition, which may also prevent the development of acquired resistant to this cancer therapy.
“We are very pleased that this phase I study has kicked off and believe that the combination of our compound with everolimus can potentially further improve the outcome for patients suffering from RCC,” said Rolland-Yves Mauvernay, President and founder of Debiopharm Group™.
“We continue to be impressed with Debiopharm’s systematic approach in developing Debio 0932 for the treatment of cancers where it is shown to have a strong scientific rationale and supportive preclinical data. We believe that potent inhibition of HSP90 by Debio 0932 with its promising safety profile and convenient oral dosing, in combination with everolimus has the potential to provide improved benefit for patients with kidney cancers,” said Ali Fattaey, Ph.D., President and Chief Operating Officer of Curis.