Tumor response data previously won Merck & Co. and partner Eisai an FDA breakthrough therapy designation for the combination of PD-1 star Keytruda and RTK inhibitor Lenvima in newly diagnosed liver cancer, but it wasn't enough for an approval.
The agency has slapped a complete response letter on the pair's application, it said Wednesday. The reason? Competitor Roche in late May set the bar high with a first-in-class green light based on more mature clinical results.
The FDA decided Merck’s and Eisai’s early data “do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic [hepatocellular carcinoma] with no prior systemic therapy for advanced disease,” the companies said.
Merck and Eisai filed with tumor response results from Keynote-524, a phase 1b, single-arm study. According to data just unveiled at this year’s American Society of Clinical Oncology virtual meeting, the combination of Keytruda and Lenvima triggered a response in 36% of previously untreated liver cancer patients, lasting for a median 12.6 months.
That improvement may have convinced the FDA before—or, at least, the two drugmakers hoped so. But Roche’s pairing of immuno-oncology agent Tecentriq and anti-VEGF drug Avastin just nabbed an FDA nod in first-line liver cancer with gold-standard life extension data.
Roche showed the Tecentriq-Avastin regimen cut the risk of death by 42% and the risk of disease progression or death by 41% compared with Bayer’s standard-of-care Nexavar in the phase 3 Imbrave150 study.
It marks not only the first such win for the PD-1/L1 class, but also the first time in a decade that a treatment has improved survival benefits in first-line liver cancer. Lenvima as a monotherapy already bears an FDA label in the same patient setting, but that nod is based on noninferiority survival data against Nexavar.
Now, the two companies are going back to work on testing the Keytruda-Lenvima combo as a first-line liver cancer therapy in the phase 3 Leap-002 study, which is already fully enrolled.
Still, the rejection means the Keytruda-Lenvima combo will have to live with a single FDA nod—in endometrial carcinoma—even longer. And it dashed Merck’s hope at a quick leap into early liver cancer use as the second-line market becomes more crowded. Most recently, Bristol Myers Squibb snagged an accelerated FDA approval for its Opdivo-Yervoy dual immuno-oncology cocktail for hepatocellular carcinoma patients who have previously received Nexavar.
Besides Lenvima, Merck is also collaborating with Bayer, pairing Keytruda with the German company’s Nexavar follow-on drug Stivarga in new liver cancer patients.