The US FDA has awarded Merck & Co a speedy review for the use of immuno-oncology drug Keytruda in combination with chemotherapy in lung cancer.
The US regulator will decide by 10 May whether to approve the combination of PD-1 inhibitor Keytruda (pembrolizumab) with pemetrexed/carboplatin as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC).
Merck is seeking approval of the combo for all-comers, in other words regardless of the patients’ PD-L1 expression or ALK and EGFR mutation status, and says approval would consolidate Keytruda’s position at the heart of NSCLC therapy.
As monotherapies checkpoint inhibitors such as Keytruda can generally only be used in a proportion of all cancer patients, but use alongside chemo would bring a much larger potential population into play.
Merck has already overtaken arch-rival Bristol-Myers Squibb in first-line NSCLC after the latter’s Opdivo (nivolumab) drug failed to show a benefit in a phase III trial reported last year, and approval alongside chemotherapy would lengthen Merck’s lead over other PD-1/PD-L1 inhibitors.
Among these, Roche’s Tecentriq (atezolizumab) is the nearest competitor having been approved for second-line NSCLC last October and with phase III trials ongoing as a first-line therapy alone and in combination with other drugs. AstraZeneca’s durvalumab and Merck KGaA/Pfizer’s avelumab are currently vying to become the fourth market entrant, both for indications other than NSCLC in the first instance.
Merck’s filing is based on the results from a subset of 123 patients from the KEYNOTE-021 trial, which showed that giving Keytruda alongside pemetrexed and carboplatin improved response rates and progression-free survival (PFS) compared to chemo alone.
After a median follow-up of 10.6 months, 55% of patients on the combination responded compared to 29% of the chemotherapy group, while PFS came in at 13 months and 8.9 months, respectively.
“Through our monotherapy and combination studies, we are working to find new approaches to help a broad range of patients with lung cancer,” said Merck’s oncology R&D head Dr Roger Dansey.
“If approved, this could be the first regimen combining chemotherapy with an immuno-oncology agent for patients with advanced NSCLC,” he added.
Analysts at Leerink said news of the filing and accelerated review was “a significant surprise” and could give Merck a leg-up in the first-line NSCLC race over AZ and BMS – both of which are developing dual immuno-oncology regimens – and Roche whose lead trial is testing Tecentriq with chemotherapy combination.