Merck targets high responders in Keytruda lung cancer filing

Merck has filed its immunotherapy drug Keytruda for use in lung cancer patients, and has pinpointed its benefits for patients who carry a special biomarker.

New data has confirmed that the drug is particularly effective at delaying progression of the disease and extending lives in patients with high levels of the PD-L1 biomarker.

Merck is in a closely-fought race with Bristol-Myers Squibb (BMS) and its rival drug PD-1 immunotherapy drug Opdivo across a range of cancers, with both already approved in advanced melanoma. Opdivo has just been approved in non-small cell lung cancer (NSCLC), but Merck hopes to make up ground on its rival by identifying patients who will benefit most.

New data from Merck's phase Ib KEYNOTE-001 trial studied the drug in 313 patients with NSCLC, some of whom had been treated previously, and some who had not.

These patients were tested to see how many of their tumour cells carried the PD-L1 protein, and showed that those with high levels of the biomarker responded best to Keytruda.

The analysis showed that patients with the highest levels of PD-L1 (expressed in more than 50 per cent of tumour cells) had an overall response rate (ORR) of 45.4 per cent. This dropped off steeply in patients with lower levels of the biomarker, down to 19.4 per cent in those who had barely any PD-L1 expression.

The company also presented data on progression free survival (PFS), which showed the highest PD-L1 expressing sub-group achieved a median PFS of 6.3 months, compared to 2.3 months in those with the lowest PD-L1 levels.

The story was similar in overall survival, with median OS not being reached in the high group, but 8.8 months for the other sub-groups.

Merck announced yesterday that it had submitted a supplemental Biologics Licence Application (sBLA) for Keytruda in advanced NSCLC with the US FDA, which is expected to accept or reject the application within 60 days. The drug was granted Breakthrough Therapy designation in advanced NSCLC by the FDA in October 2014.

Both Keytruda and Opdivo are tipped to earn billions in peak revenues, but neither company has opened up a clear lead in the market.

As with all targeted therapies, the PD-L1 test needs a companion diagnostic to be developed and approved. Dako North America (part of Agilent) has submitted a Premarket Approval Application (PMA) for an immunohistochemistry companion diagnostic test that detects PD-L1 expression.

Meanwhile on Friday, BMS announced that its CheckMate -057 trial of Opdivo in NSCLC had been stopped early. The open-label, randomised phase III study looked at the drug versus docetaxel in previously treated patients with advanced non-squamous NSCLC, and was halted early because the drug showed superior overall survival in patients compared to the control arm.

The news is part of a new wave of data being presented by companies at the American Association for Cancer Research (AACR) Annual Meeting in Philadelphia. Merck has also released new data showing Keytruda works in patients with advanced pleural mesothelioma, a rare lung cancer, and also presented a study showing it achieved superior overall survival in advanced melanoma patients compared to BMS's Yervoy.