Trial of ARO-HIF2 for Clear Cell Renal Cell Carcinoma Announces Positive Interim Results

The trial has successfully enrolled 17 patients with clear cell renal cell carcinoma and has reported that the drug is well tolerated at doses of up to 525 mg weekly.

A phase 1b dose-finding study of ARO-HIF2 for the treatment of patients with clear cell renal cell carcinoma (ccRCC) has successfully enrolled 17 patients and has shown that the drug is well tolerated at doses of up to 525 mg weekly, according to a press release.

“The AROHIF21001 phase 1b study is designed to evaluate safety as well as preliminary pharmacodynamics and efficacy in an advanced ccRCC patient population,” said James Hamilton, MD, MBA, senior vice president of discovery and translational medicine at Arrowhead, in the press release. “We believe that in the first 2 dose cohorts investigational ARO-HIF2 is showing clear signs of meaningful target engagement and some potentially early signs of efficacy in at least 1 patient.”

ARO-HIF2 is an investigational RNA interference therapeutic. Arrowhead is currently enrolling the third planned patient cohort for the trial and intends to present addition data soon. According to the press release, 17 patients have been enrolled to receive intravenous injections of either 225 mg weekly (cohort 1, n=7) or 525 mg weekly (cohort 2, n=10). Cohort 3 is currently enrolling patients to receive 1050 mg weekly.

Investigators assessed the HIF2α protein H-score and found that 9 out of 17 patients had tumor samples that could be evaluated. Seven of those patients demonstrated reductions in HIF2α and reductions ranged from -9% to -82% with a mean reduction of -48%.

Efficacy of the drug was assessed using the Response Evaluation Criteria in Solid Tumors. In cohort 2, one person had a partial response with approximately 65% tumor shrinkage and 5 had a best response of stable disease. Furthermore, 4 subjects in cohort 2 remain on the drug with stable disease, with treatment durations between 12 and 24 weeks.

As of the reporting date, the investigational drug has been generally well tolerated at doses up to 252 mg weekly. No cases of anemia related to the drug have been reported.

“Tumors typically have a high level of heterogeneity and the patients in AROHIF21001 have advanced ccRCC and have failed multiple lines of treatment including checkpoint inhibitors and anti-VEGF regimens, so these early results in a heavily pre-treated population are encouraging for investigational ARO-HIF2 and our tumor-targeted platform broadly,” Hamilton said in the press release. “ARO-HIF2 has been generally well-tolerated, and we look forward to continued dose escalation.”

REFERENCE

Arrowhead Announces Positive Interim Results Phase 1b Study of ARO-HIF2 for Treatment of Clear Cell Renal Cell Carcinoma. News release. BusinessWire. July 6, 2021. Accessed July 9, 2021. https://www.businesswire.com/news/home/20210706005215/en/Arrowhead-Announces-Positive-Interim-Results-from-Phase-1b-Study-of-ARO-HIF2-for-Treatment-of-Clear-Cell-Renal-Cell-Carcinoma