“Following promising activity in the dose-escalation stage, I am further encouraged by the anti-tumor activity observed in the monotherapy expansion cohort suggesting that zanzalintinib may be an effective therapy following disease progression after prior treatments,” said Sumanta Pal, M.D., Clinical Professor, City of Hope Comprehensive Cancer Center, who is presenting the findings. “Many of these patients with advanced kidney cancer have exhausted their treatment options, having progressed on both immune checkpoint inhibitors and tyrosine kinase inhibitors including cabozantinib, so these results showing strong response rates and durable responses are encouraging for this group of patients.”In this ccRCC cohort, 97% of patients had received prior immunotherapy and 81% had received prior VEGFR-tyrosine kinase inhibitor (TKI), including 53% who had received cabozantinib. Eighty-one percent of patients were intermediate risk by International Metastatic RCC Database Consortium.
At a median follow-up of 8.3 months, 12 of the 32 patients enrolled in the expansion cohort had a confirmed partial response for an objective response rate of 38%; the disease control rate was 88%. Additional efficacy outcomes by prior therapy subgroups are shown in Table 1.
At data cutoff, 50% of patients were continuing treatment. The median duration of response was 7.4 months for the cabozantinib-naïve group and not estimable for the cabozantinib-exposed group.
“These findings underscore the potential zanzalintinib may hold for patients with refractory kidney cancer, including those who have previously progressed on cabozantinib,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “As STELLAR-001 and our phase 3 STELLAR trials progress, we look forward to elucidating the potential of zanzalintinib in kidney cancer as well as in other advanced solid tumors.”The safety population (n=81) included 32 patients from the ccRCC expansion cohort treated at 100 mg plus 49 patients across different solid tumors from the dose-escalation stage who received single-agent zanzalintinib at doses ranging from 10-140 mg. The safety profile was similar between the ccRCC cohort and the safety population. Discontinuations due to treatment-related adverse events (AEs) occurred in 9% of patients in the ccRCC cohort and 12% of patients in the safety population. There were three grade 5 treatment-emergent AEs in the ccRCC cohort and two more in the safety population; none were treatment-related, nor was the single grade 4 event. Of note, the rate of palmar plantar erythrodysesthesia was low with zanzalintinib (9% in the ccRCC cohort and 12% in the safety population, all grade 1-2).
About STELLAR-001
STELLAR-001 (NCT03845166) is a global, open-label phase 1b/2 study of zanzalintinib as a single agent or in combination with atezolizumab in patients with inoperable locally advanced or metastatic solid tumors. The trial is divided into two parts: a dose-escalation stage and an expansion cohort stage. The expansion cohorts evaluating zanzalintinib as a single agent or in combination with atezolizumab include patients with ccRCC, non-clear cell RCC, breast cancer that is hormone receptor-positive and HER-2 negative, castration-resistant prostate cancer and colorectal cancer. More information about the trial is available at ClinicalTrials.gov.
About Zanzalintinib
Zanzalintinib is a next-generation oral TKI that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL, and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including genitourinary, colorectal, and head and neck cancers.
Zanzalintinib is not approved for ccRCC.
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.
About Exelixis
Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by bi-coastal centers of discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates, and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook, and follow Exelixis on LinkedIn.
Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis.
_____________________________
- Key Statistics About Kidney Cancer. American Cancer Society website. Available at: https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html. Accessed November 2023.
- What Is Kidney Cancer? American Cancer Society website. Available at https://www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html. Accessed November 2023.
- Survival Rates for Kidney Cancer. American Cancer Society website. Available at https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/survival-rates.html. Accessed November 2023.