This morning has brought another positive development in the rapidly changing treatment landscape for lung cancer. Merck reported that a combination regimen utilizing its immunotherapy drug, pembrolizumab (Keytruda), has succeeded in a confirmational Phase 3 study.
Merck (NYSE: MRK) said that a trial in which 614 patients just diagnosed with non-small cell lung cancer got pembrolizumab and two chemotherapies, pemetrexed (Alimta) and either cisplatin or carboplatin, met both of its main goals. Upon an interim look of the study, Keynote-189, the three-drug combination kept tumors from spreading longer than the two chemotherapies alone, and also helped people live longer, Merck said. Final results from Keynote-189 aren’t expected until 2019.
Merck hasn’t, however, disclosed the magnitude of the benefit produced by the combination, and didn’t discuss the side effects except to report that they were “consistent with [what has been] previously observed.” This information, to be shared at an unspecified future medial meeting, is critical to help understand the benefits and risks of taking the combination. As promising as new immunotherapies like pembrolizumab have been, the side effects in combination with other agents have been disconcerting, as Xconomy reported in 2017.
The FDA approved the pembrolizumab-chemotherapy combination on an “accelerated” basis, on a thinner body of evidence than normal, in May 2017. The Keynote-189 study is a confirmational trial Merck will use to uphold the original approval decision. Merck shares climbed more than 5.5 percent in pre-market trading on Tuesday. Shares of rival Bristol-Myers Squibb (NYSE: BMY) fell about 2 percent.
The study is one of several trials set to produce data in 2018 that, if positive, could continue to change how lung cancer is treated. Lung cancer is the second most common cause of cancer, behind skin cancer, and is the leading cause of cancer-related deaths, according to the American Cancer Society. The ACS predicts 234,030 new cases and 154,050 deaths from the disease this year alone. NSCLC is the most common form of lung cancer, accounting for 80 to 85 percent of cases, according to the ACS.
Cancer immunotherapy drugs have been working their way forward as important treatments for a variety of cancers, but lung cancer is a particularly competitive field. First, in October 2015, the FDA approved Bristol’s immunotherapy drug nivolumab (Opdivo) and Merck’s pembrolizumab within days of one another for patients whose NSCLC spread after chemotherapy. Then in 2016, pembrolizumab succeeded in a Phase 3 trial in newly diagnosed lung cancer patients, but nivolumab failed. Merck went on to have the first FDA-approved immunotherapy for those with a particular form of the disease that featured an abnormally high amount of the protein PD-L1.
Still, these drugs on their own only work in a small fraction of patients. The race is on to do better, and that means testing pembrolizumab and nivolumab in combination with chemotherapies, other immune system-boosting drugs, and more.
So far, immunotherapy-chemotherapy combinations have shown promise. Months after the FDA granted accelerated approval to the pembrolizumab-chemotherapy combination, for instance, Roche/Genentech touted success in a Phase 3 study, IMpower150, testing a combination of its immunotherapy atezolizumab (Tecentriq), another one of its cancer drugs, bevacizumab (Avastin), and chemotherapy in lung cancer.
Important developments on that front are on tap for 2018, among them the coming specifics from the Keynote-189 trial. Another noteworthy development will be how long the Roche/Genentech drug combination in IMower150 is shown to extend patients’ lives. Then there are the expected results from a 2,220-patient Phase 3 trial called Checkmate-227, which combines Bristol’s nivolumab with another of its immunotherapies, ipilimumab (Yervoy), in patients newly diagnosed with NSCLC. The combination is already approved in melanoma, but resounding success in NSCLC could mark another leap forward for immunotherapy. An update could come this month. AstraZeneca (NYSE: AZN) should also update a study, Mystic, that similarly combines two immunotherapy drugs, durvalumab (Imfinzi) and tremelimumab.
Evercore ISI analyst Umer Raffat noted that, given the success of Keynote-189 and IMpower150, immunotherapy-chemotherapy combinations are “now the bar to beat” for experimental two-drug immunotherapy regimens in lung cancer.
“We see these results as further solidifying [Merck’s] current lead position in the first-line NSCLC race,” added Leerink biopharma analyst Joseph Schwartz, in a note Tuesday morning. “However, full data (to be presented at an upcoming meeting) will be necessary to compare with” the upcoming full results of IMpower150, Checkmate-227, and Mystic, he wrote.
Here’s more on cancer immunotherapy, and how drug combinations are being advanced through clinical testing.