The relentless march of Merck & Co/MSD’s cancer immunotherapy Keytruda into mega-blockbuster territory took another step forward this week, but had a stumble.
The positive news for Merck was that the FDA has started its priority review of Keytruda (pembrolizumab) in its first small cell lung cancer (SCLC) indication, as the company tries to press its already-dominant position in non-small cell lung cancer (NSCLC), the more common form.
The application is for accelerated approval based on the results of the KEYNOTE-158 trial, which showed that Keytruda, given as a monotherapy to SCLC patients whose cancer had progressed despite two or more lines of prior therapy, had an objective response rate (ORR) of just under 19%, including 3% complete responses.
It’s the second priority review filing for Keytruda to get underway at the FDA in a week, coming after the PD-1 inhibitor was filed as a first-line treatment for head and neck cancer both as a monotherapy and in combination with chemotherapy.
The SCLC data were presented at last year’s ASCO meeting, at which Merck suggested that the data was an incentive to start testing Keytruda alongside chemotherapy as a first-line treatment for SCLC, which has a five-year survival rate of only 6%.
The drug is now being studied in combination with chemotherapy in the phase 3 KEYNOTE-604 study in patients with newly-diagnosed, extensive stage SCLC.
Liver failure
On the downside, Merck also revealed this week that the phase 3 KEYNOTE-240 trial of the checkpoint inhibitor in hepatocellular carcinoma – the most common form of liver cancer – failed to show an increase in survival compared to placebo and supportive care in patients previously treated with Bayer’s targeted therapy Nexavar (sorafenib).
Keytruda was given accelerated approval by the FDA for that indication in November based on response rate data, so it remains to be seen whether the FDA will maintain the licence for Keytruda in second-line advanced HCC in light of the new survival readout.
In a statement, Merck’s head of R&D Roy Baynes said the results of the phase 3 trial were “generally consistent with findings from the phase 2 study, KEYNOTE-224, which led to the accelerated approval.”
The rare setback for Keytruda comes as it has started to show signs of lengthening its new lead in the PD1/PD-L1 inhibitor category over main rival Bristol-Myers Squibb and others, fuelled by its dominance of the big first-line NSCLC market and emerging position in other cancers including those affecting the kidney, oesophagus, head and neck and bladder.
The slip means that BMS has an opportunity to claw back some territory for Opdivo (nivolumab), which got an accelerated approval in HCC towards the end of 2017 and is hoping to move its drug into first-line use based on the CheckMate-459 study which pits Opdivo against Nexavar.