Casdatifan for the Treatment of Refractory Metastatic Clear Cell Renal Cell Carcinoma
brief summary
This is a single-institution, pilot study of oral casdatifan, a selective HIF-2α inhibitor, in patients with metastatic clear cell renal cell carcinoma refractory to prior IO- and VEGF-based therapies. This phase I trial evaluates the effects of casdatifan on certain genes linked to kidney cancer growth and tests it for the treatment of clear cell renal cell cancer that has not responded to previous treatment (refractory) and that has spread from where it first started (primary site) to other places in the body (metastatic). Casdatifan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
detailed description
PRIMARY OBJECTIVE:
I. To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory clear cell renal cell carcinoma (ccRCC) population.
SECONDARY OBJECTIVES:
I. To assess changes in global tumor gene expression following casdatifan treatment.
II. To identify differences in baseline and on-treatment HIF-mediated gene expression between objective responders and non-responders.
OUTLINE:
Patients receive casdatifan orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study.
Two dose reductions will be permitted in the event of drug-related adverse events, per protocol-defined criteria:
* Reduced dose (-1): 50mg once daily * Reduced dose (-2): 25mg once daily Treatment will be discontinued if toxicity is not manageable at this reduced dose.
After completion of study treatment, patients who discontinue treatment for reasons other than disease progression are followed up every 12 weeks thereafter.
Casdatifan will be provided by Arcus. No additional therapeutic agents will be administered as part of this protocol.
official title
A Pilot Study of HIF-Mediated Gene Expression Changes in Casdatifan-Treated Refractory Renal Cell Carcinoma