Xcovery pitted its ALK inhibitor against Pfizer’s Xalkori—the first-ever FDA-approved drug in its class—and came out on top. The drug, ensartinib, shrank tumors in three-quarters of previously untreated lung cancer patients, compared to Xalkori’s 67%, and staved off cancer for two years, more than double the time Xalkori logged.
The phase 3 study tested ensartinib as a firstline treatment against Xalkori (crizotinib) in 290 patients with ALK-positive non-small cell lung cancer. As of July 1, ensartinib had shrunk the tumors of 75% of patients, topping Xalkori's 67% mark. And even though Xalkori did unusually well in the study, keeping cancer at bay for a median of 12.7 months, Xcovery’s drug trounced it with median progression-free survival of 25.8 months. The median overall survival—how long the drug extended patients’ lives—had not been reached.
“Interestingly, crizotinib overperformed in the study; the duration of response for patients on crizotinib was 27.3 months, which is much higher than what we’ve seen in other studies for patients on crizotinib,” said Leora Horn, M.D., director of the Thoracic Oncology Program and a professor at the Vanderbilt-Ingram Cancer Center, who presented the study.
“It was the best performance ever done by crizotinib in any randomized study" in previously untreated patients, said Xcovery Chief Medical Officer Giovanni Selvaggi, a thoracic oncologist by training who previously worked on Novartis’ ALK inhibitor Zykadia.
Ensartinib also did better than Xalkori in a small group of patients whose disease had spread to the brain. All 11 patients whose brain tumors were large and defined enough to be seen on a scan saw their tumors shrink, Selvaggi said. Seven of the 11 patients (64%) had enough shrinkage to be considered responders, compared to just one-fifth of the 19 patients on Xalkori.
The most common side effect was a sunburn-like rash, “a new toxicity” for ALK inhibitors, Horn said.
“It’s a very benign rash that can be compared to a sunburn and it normally goes away with continued treatment and topical therapies,” Selvaggi said. Unlike the rash that comes with meds that target EGFR, which often gets worse the longer patients take the drug, patients taking ensartinib do not need to stop treatment to get rid of the rash, he added.
The study started enrolling patients who were tested for the ALK mutation in local laboratories but about 40 patients in, it switched over to recruiting those who were centrally tested at larger labs, Horn said. It did this to cut down on false positive results from local testing. Of the 43 patients who were locally tested, 11 were thought to be ALK-positive before central testing showed they were actually negative; seven received ensartinib and two got Xalkori, Horn said.
“Since we only target the ALK protein with this drug, if patients are ALK-negative, it would not be expected to slow tumor growth,” Selvaggi said.
Understandably, the false positive patients would skew the data, so the investigators also reported results for what they called a modified intent-to-treat population of only centrally tested patients. The progression-free survival for this group had not been reached by the data cutoff, meaning more than half of the patients did not see their cancer worsen by then. This figure stayed at 12.7 months for patients on crizotinib.
Up next? Discussing the data with regulators and eventually, a filing: “We are excited to bring an effective and safe new option to patients and their physicians and therefore we are planning to share the data with regulatory agencies as our next step," Selvaggi said. It's been a long time coming for the Scripps Florida spinout that made the Fierce 15 class of 2007.
The thing is, if ensartinib can ultimately win approval, it'll have more drugs to battle than just Xalkori. Roche's Alecensa, the class' current sales leader, and Zykadia both topped Xalkori on their way to earning first-line approvals in 2017, and Pfizer's Lorbrena—Xalkori's follow-up med—earlier this week posted top-line results showing it could beat out its predecessor, too.