Merck KGaA and Pfizer have staked a claim to the first-line renal cell carcinoma market, with data on a new combination that analyst say could challenge to become a new standard for the disease.
The JAVELIN Renal 101 study reported at this week’s ESMO conference paired Merck’s immuno-oncology drug Bavencio (avelumab) with Pfizer’s tyrosine kinase inhibitor Inlyta (axitinib), and revealed a 39% reduction in progression-free survival (PFS) for the duo versus Pfizer’s Sutent (sunitinib), which has been the reference standard for first-line RCC treatment for a decade, in PD-L1-positive patients.
There was a significant benefit regardless of whether the patients’ tumours expressed the PD-L1 biomarker, with the ‘all-comer’ group seeing a 31% reduction in PFS versus Sutent, and the effects of the combination were consistent across patients with favourable, intermediate, and poor prognoses.
Combine that with the positive data reported last week with the combination of Merck & Co/MSD’s Keytruda (pembrolizumab) and Inlyta in the KEYNOTE-426 trial and the combination of checkpoint inhibitor and TKI has emerged as an “early winner… against the backdrop of thousands of combination studies” in RCC, according to William Blair’s Andy Hsieh.
“While the overall survival data are not mature, we are impressed by the high response rate, low frequency of progressive disease, and tolerable safety profile, highlighted by low discontinuation rate,” he writes in a research note.
Merck already has overall survival data in hand for the Keytruda/Inlyta combination, giving it an edge among the immuno-oncology/TKI combinations, but Hsieh thinks it is likely that Bavencio/Inlyta will also hit this endpoint.
Both combinations could challenge the position of Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab), which has started to replace Sutent and other TKIs like Exelixis’ Cabometyx (cabozantinib) as the standard of care in first-line RCC. However, it’s notable that Opdivo/Yervoy only topped Sutent when it came to intermediate- and poor-risk patients and not the good-prognosis group, so Bavencio/Inlyta’s across-the-board benefit of could be an advantage.
Exelixis’ drug could also be threatened by the combination data, although Hsieh reckons that could be short-lived.
Cabometyx has made big gains in the first-line RCC market on the back of the CABOSUN trial, which made it the only TKI in the RCC space to show both an overall survival and PFS benefit over an active comparator, and that profile “bodes well for the prospect of the ongoing phase 3 CheckMate-9ER study” of Cabometyx plus Opdivo, which is due to read out next year, he suggests.
“Taken together, while checkpoint inhibitors are now the standard of care in frontline RCC, PD-L1-positive patients tend to derive the most benefit,” notes Hsieh.
“In our view, combination with TKI could expand the clinical benefit of checkpoint inhibitors to PD-L1 negative patients.”