- The Food and Drug Administration has delayed a decision on approval of Merck & Co.'s Keytruda as monotherapy in first-line treatment of locally advanced or metastatic PD-L1-expressing non-small cell lung cancer (NSCLC). The new action date, pushed back by three months, will be April 11, 2019.
- The delay stems from Merck's submission of additional data and analyses, which the FDA judged to constitute a major amendment to the company's Supplemental Biologics License Application.
- Merck's sBLA, based on data from the Phase 3 KEYNOTE-042 trial, was granted priority review for this indication in September. The application's original Prescription Drug User Fee Action date had been set for January 2019.
The KEYNOTE-042 study, presented this year at the annual meeting of the American Society of Clinical Oncology, showed Keytruda (pembrolizumab) first-line monotherapy significantly increased overall survival compared with standard-of-care in all PD-L1-positive patients with locally advanced or metastatic non-squamous or squamous NSCLC.
These results have potential to expand Keytruda's label in first-line NSCLC monotherapy beyond its earlier frontline approvals in patients expressing PD-L1 levels of 50% or more. Now, however, a decision on expansion will have to wait a little longer.
Physicians looking to prescribe Keytruda to low-expressing PD-L1 patients already have some options. The immunotherapy has already been approved in combination with Alimta (pemetrexed) and platinum chemotherapy for the first-line treatment of patients with metastatic non-squamous NSCLC and in combination with carboplatin and either paclitaxel or nab-paclitaxel in squamous NSCLC. Both of those approvals are for any PD-L1 status.
While the PDUFA postponement is a ding to Merck, the same has happened to rival checkpoint inhibitors in recent months.
Roche's Tecentriq (atezolizumab) had its review pushed back three months, also because of a major amendment — though the drug has since received first-line approval for non-squamous NSCLC in combination with Avastin (bevacizumab) and chemotherapy.
The FDA also delayed a decision on Bristol-Myers Squibb's combination of Opdivo (nivolumab) and Yervoy (ipilimumab) in first-line NSCLC too, because the agency needed more data from the CheckMate-227 study, including an overall survival analysis of patients with low levels of a biomarker known as tumor mutational burden.
Elsewhere, Keytruda has picked up a number of FDA approvals over the past six months, securing an OK in cervical cancer, primary mediastinal large B-cell lymphoma, hepatocellular carcinoma and, most recently, metastatic Merkel cell carcinoma.