Bristol Myers' Opdivo notches a double win against chemo in esophageal cancer, potentially setting up 1st-line nod
Bristol Myers Squibb is one of a group of drugmakers prepping for a tense FDA adcomm later this month to review a host of accelerated approvals. Looking to start the month on the right note, the drugmaker rolled out new data for its PD-(L)1 checkpoint inhibitor Opdivo showing more promise in esophageal cancer.
Opdivo in combination with chemotherapy and a combination of Opdivo and Yervoy beat out chemo alone in extending the lives of first-line esophageal squamous cell carcinoma patients whose tumors are metastatic or can’t be surgically removed, according to interim results released Thursday.
A combination of Opdivo and chemo hit its primary OS and PFS endpoints over chemo alone in PD-(L)1 expressing tumors at a prespecified check-in on the Phase III CHECKMATE-648 study. Meanwhile, Opdivo plus Yervoy showed more mixed results, hitting its OS primary endpoint but missing the PFS co-primary endpoint, Bristol Myers said.
Bristol Myers is touting the results as the first time a PD-(L)1 checkpoint inhibitor has shown first-line efficacy across all upper GI tumor locations, including in the stomach, gastroesophageal junction, and esophagus. The study backed up results from CHECKMATE-649, which tested Opdivo plus chemo in first-line patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.
The FDA agreed to review results from that study as part of a priority review granted in February, with an action date set for May 25. Earning a nod in those early patients would be a clear leg up on Merck’s superstar checkpoint inhibitor Keytruda, which sports an approval in third-line patients with the PD-(L)1 biomarker dating back to September 2017 but has since flopped confirmatory trials in first- and second-line use.
CHECKMATE-648 is another win under Bristol Myers’ belt as it prepares for a three-day adcomm in April to review a broad range of immune checkpoint indications with accelerated approvals that flopped confirmatory studies, including a single Opdivo indication.
In December, Bristol walked on Opdivo’s third-line-or-later FDA approval for small-cell lung cancer after confirmatory trials for an accelerated nod in that indication back in 2018 failed to show benefit in extending patients’ lives. Based on findings from its Checkmate-451 and -331 trials, which found Opdivo failed to hit its OS primary endpoints as both a monotherapy and combo treatment with Yervoy, Bristol decided to pull its approval based on the FDA’s recommendations to follow post-marketing science.
Just a week before that, Bristol opted to forgo its chances in brain cancer glioblastoma, another chronically difficult-to-treat indication, following multiple clinical fails. The drugmaker admitted a combo of Opdivo on top of standard-of-care temozolomide plus radiation couldn’t beat placebo in extending overall survival in patients with newly diagnosed MGMT-positive glioblastoma multiforme who previously had their tumor surgically removed.