New trial data for Keytruda in triple-negative breast cancer

Merck & Co – known as MSD outside the US and Canada – has revealed additional data for its blockbuster immunotherapy for high-risk, early-stage triple-negative breast cancer (TNBC) following a recent US Food and Drug Administration (FDA) rejection in this indication.

TNBC is an aggressive and hard-to-treat subtype of breast cancer, representing around 15% of all breast cancer worldwide, approximately 300,000 cases every year. Patients who are PD-L1 positive represent a subgroup of about 40% of this total.

The new results – from the phase 3 KEYNOTE-522 trial – showed that Keytruda (pembrolizumab) met the dual-primary endpoint of event-free survival (EFS) for the treatment of high-risk early-stage TNBC patients.

Although detailed results were not revealed, Merck & Co said that, based on an interim analysis, neoadjuvant Keytruda plus chemotherapy showed a statistically significant and clinically meaningful improvement in EFS compared to chemotherapy alone.

“Keytruda is the first immunotherapy to show positive results for event-free survival in patients with high-risk early-stage TNBC, a particularly aggressive form of breast cancer,” said Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.

In 2019, Merck & Co revealed analysis of pathologic complete response (pCR) rates from Keynote-522, showing a statistically significant increase in this marker for Keytruda plus chemotherapy compared to chemotherapy alone in the same TNBC patient population, regardless of PD-L1 status.

In March 2021, the US Food and Drug Administration (FDA) issued Merck & Co a complete response letter (CRL) rejecting a supplemental biologics licence application (sBLA) in TNBC, based on the pCR data and early interim EFS findings.

The FDA’s oncologic drugs advisory committee (ODAC) voted 10-0 that a regulatory decision for Keytruda in early-stage, high-risk TNBC patients should be delayed until further data from KEYNOTE-522 became available.

“The improvement in pathological complete response rates initially observed following pre-operative treatment was encouraging, and now that we are seeing the data mature after four years to include a statistically significant improvement in event-free survival, we look forward to working with the FDA and other global authorities to bring this new option to patients as quickly as possible,” commented Baynes.