Arrowhead Pharmaceuticals has started dosing patients in a Phase Ib AROHIF21001 clinical trial of ARO-HIF2 to treat clear cell renal cell carcinoma (ccRCC).
ARO-HIF2 is an experimental RNA interference (RNAi) therapeutic intended to inhibit the generation of HIF-2α, which is associated with tumour progression and metastasis in ccRCC.
The dose-finding Phase Ib trial will assess the safety of the drug candidate and establish the recommended Phase II dose in up to 18 patients with advanced ccRCC.
Secondary objectives of the trial include pharmacokinetics and preliminary efficacy, determined using Response Evaluation Criteria in Solid Tumors (RECIST).
Meanwhile, exploratory objectives are post-dose tumoural expression of HIF genes in response to treatment with ARO-HIF2 and change in Karnofsky Performance Status (KPS).
The study will also track tumour response and serum biomarkers of the drug candidate’s activity, as well as assess plasma and urine metabolites, among others.
The trial is expected to be completed in 2022.
Arrowhead Pharmaceuticals chief medical officer Javier San Martin said: “This Phase Ib study is designed to provide us with a robust readout on safety and dose response of ARO-HIF2, and may also deliver signals on preliminary efficacy in an advanced ccRCC patient population.
“We believe that HIF-2α is an attractive target for RNAi-based gene silencing and, more broadly, we are eager to achieve clinical validation for our tumour targeted TRiM-enabled RNAi therapeutics so we can address additional unmet needs in oncology.”
In March this year, Arrowhead started dosing in a Phase I/II trial (AROHSD1001) of ARO-HSD for the treatment of patients suffering from alcohol and non-alcohol related liver diseases.
AROHSD1001 is designed to investigate the safety and efficacy of ARO-HSD in approximately 74 healthy participants with nonalcoholic steatohepatitis (NASH) or suspected NASH.