Savolitinib not significantly efficacious in advanced clear cell renal cancer
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CHICAGO — Savolitinib, alone or in combination with durvalumab, did not demonstrate significant efficacy in patients with advanced clear cell renal cancer, according to a presentation at ASCO Annual Meeting.
“We know drugs like cabozantinib have multiple activities, including MET, but savolitinib is a potent mass inhibitor. And so it has an established dose, and exploring it in metastatic clear cell renal cancer is reasonable,” Thomas Powles, MBBS, MRCP, MD, professor of genitourinary oncology, lead for solid tumor research and director of Barts Cancer Centre at St. Bartholomew's Hospital in London, England, said during the presentation. “We know more about CTLA-4. Tremelimumab is a CTLA-4 inhibitor, but again, it's not been widely explored in metastatic clear cell renal cancer.”
“So, in this study, we explored the combination of savolitinib-durvalumab or tremelimumab-durvalumab in VEGF-resistant clear cell [renal cancer]. Durvalumab alone is included as a component part, and we also explore a number of biomarkers in a subset of this study.”
Between 2017 and 2021, Powles and colleagues included 139 patients with advanced clear cell renal cancer, who had previously received VEGF targeted therapy but not immune checkpoint inhibitors or MET inhibitors, within the study. They randomized patients to receive either durvalumab (D), savolitinib (S), durvalumab and tremelimumab (DT), or durvalumab and savolitinib (DS). The primary endpoint of the study was confirmed response rate, with a response rate of at least 50% required for further exploration. Researchers closed the S arm early due to a lack of efficacy.
The primary endpoint was not met in any of the four arms, with confirmed response rates of 10% in D, 5% in S, 28% in DT and 13% in DS. In MET-driven patients, confirmed response rates were 0%, 0%, 50% and 17%, respectively.
Median OS was found to be 26.1 months (80% CI, 16.2–32.0) in D, 23.1 months (80% CI, 20.6–29.7) in S, 21.9 months (80% CI, 16.3–31.5) in DT and 16.1 months (80% CI, 10.3–18.8) in DS, with 12-month PFS rates of 26% (80% CI, 17-36), 21% (80% CI, 10-35), 33% (80% CI 24-43) and 17% (80% CI, 10-26), respectively.
Grade 3 or more treatment-related adverse events were reported in 10% of D, 26% of S, 23% of DT and 23% of DS, with one treatment-related death also occurring in DT.
“Savolitinib alone, or in combination with durvalumab, did not meet predefined activity levels. This also appeared to be the case in MET-driven tumors,” Powles said. “The addition of tremelimumab to durvalumab did not clearly improve efficacy.”
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Powles T, et al. Abstract LBA4503. Presented at: ASCO Annual Meeting, June 3-7, 2022, Chicago.
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