Merck tries again in adjuvant breast cancer

An early cut of the Keynote-522 trial, of Keytruda in neoadjuvant and adjuvant triple-negative breast cancer, was not enough to win the checkpoint blocker FDA approval earlier this year: Merck received a complete response letter in the wake of a negative adcom. But a hit on the study’s co-primary endpoint, announced today, means that the company is heading straight back to regulators for a second shot. An interim analysis found a “statistically significant and clinically meaningful” improvement in event-free survival (EFS), Merck said. At least three previous interim looks had failed to find a statistical showing on this measure, and Merck had tried to win approval largely on the other co-primary, pathological complete response (pCR); despite a statistically very sound readout on pCR, this surrogate measure is considered to provide more questionable evidence of effectiveness than does EFS. The hit on a survival endpoint should put the application on better footing – though it is not inconceivable that the FDA will want to wait for longer cuts of the data, or possibly the final readout. That will depend on the strength of the EFS finding, and for now Merck is keeping that under wraps.

Ongoing trials of Keytruda in perioperative breast cancer settings
Study  Disease   Results
Keynote-522 TNBC pCR: 64.8% vs 51.2% (p=0.00055). EFS: hit significance at 4mth interim, data TBD
Keynote-756 ER+/HER2- breast cancer Still recruiting, interim readouts planned. Primary completion 2031
NCI-sponsored TNBC Still recruiting, interim readouts likely. Primary completion 2026
TNBC=triple negative breast cancer. Source: Evaluate Pharma and clinicaltrials.gov.

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