ASCO GU 2022: Renal Cell Carcinoma Highlights

Phase II study of neoadjuvant cabozantinib in patients with locally advanced non-metastatic clear cell renal cell carcinoma

Based on the findings from the Phase II study (NCT04022343), neoadjuvant cabozantinib was safe and induced a reduction in tumor size in all patients with locally advanced nonmetastatic ccRCC. According to the results from the analysis, 17 patients with biopsy-proven clear-cell RCC were treated with neoadjuvant cabozantinib at a starting dose of 60 mg once per day for 12 weeks. 

The results of this investigation revealed that all of the patients’ tumors had shrunk. Five patients (29.4%) experienced a partial response, while 12 patients had stable disease. The patients who were given cabozantinib did not experience disease progression. The original kidney tumor was shrunk by a median of 23%. Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced nonmetastatic clear-cell RCC.

Analyst opinion: A larger clinical trial is needed to further establish the role of presurgical treatment in Renal Cell Carcinoma. This will allow us to understand the long-term role of those treatments. Considering that researchers have already witnessed the increased response rates with Cabozantinib in the metastatic setting and the drug has now shown a safe response in the neoadjuvant setting, we look forward to some exciting data in late phase trial as well.

Moreover, we also know that Neoadjuvant treatment is well established in different solid tumors such as breast cancer, gastrointestinal cancers, and others, and now it’s time for Cabozantinib to enter this area with high unmet need for Renal Cell Carcinoma patients.

Positive Interim results from the Phase I study of ARO-HIF2 to silence HIF2-alpha in patients with advanced ccRenal Cell Carcinoma (AROHIF21001)

Arrowhead Pharmaceuticals announced the positive interim results from AROHIF21001 (NCT04169711), a Phase Ib dose-finding clinical study of ARO-HIF2 being developed as a treatment for patients with clear cell renal cell carcinoma (ccRCC). According to the results presented at the ASCO GU symposium, ARO-HIF2 provides initial proof of target engagement based on reductions in hypoxia-inducible factor-2 alpha (HIF2α) expression, and the safety profile of HIF-2 was well tolerated. From the efficacy point of view, the disease control rate (DCR) in all the three cohorts was 39%. With the data cut off as December 1, 2021, the ORR was 8%, with one patient in Cohort 2 and one patient in Cohort 3 achieving a partial response in the defined criteria.  From the safety point of view, ARO-HIF2 was generally well-tolerated in patients. To draw the inference, the interim safety and efficacy results of ARO-HIF2 are promising to treat patients with advanced ccRCC, and there is a space in the market for such assets.