Merck’s Keytruda showed increase in pathological complete response with chemotherapy versus neoadjuvant therapy chemotherapy in early-stage triple-negative breast cancer

Merck’s trial of Keytruda plus chemotherapy, followed by adjuvant Keytruda as monotherapy, which was granted Breakthrough Therapy designation (BTD) by the U.S. Food and Drug Administration (FDA) for the neoadjuvant treatment of patients with high-risk, early-stage TNBC plus chemotherapy, resulted in a statistically significant increase in pathological complete response (pCR) versus chemotherapy.

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #ESMO19–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results from the pivotal neoadjuvant/adjuvant Phase 3 Keynote-522 trial in patients with early-stage triple-negative breast cancer (TNBC). The trial investigated a regimen of neoadjuvant Keytruda, Merck’s anti-PD-1 therapy, plus chemotherapy, followed by adjuvant Keytruda as monotherapy (the Keytruda regimen) compared with a regimen of neoadjuvant chemotherapy followed by adjuvant placebo (the chemotherapy-placebo regimen). Interim findings – which are from the first randomized trial of an anti-PD-1 therapy in the neoadjuvant/adjuvant setting for TNBC – are being presented today during the Presidential Symposium at the European Society for Medical Oncology (ESMO) 2019 Congress (Abstract #LBA8).

In the neoadjuvant phase, Keytruda plus chemotherapy (n=401) resulted in a statistically significant increase in pathological complete response (pCR) versus chemotherapy (n=201), from 51.2% with neoadjuvant chemotherapy to 64.8% for neoadjuvant Keytruda plus chemotherapy, in patients with early-stage TNBC (p=0.00055). Pathological complete response, one of the dual primary endpoints was defined as ypT0/Tis ypN0 (i.e., no invasive residual cancer in breast and lymph nodes). The improvement seen when adding Keytruda to neoadjuvant chemotherapy was observed regardless of PD-L1 expression. In the other dual primary endpoint of event-free-survival (EFS), with a median follow-up of 15.5 months, the Keytruda regimen reduced the risk of progression in the neoadjuvant phase and recurrence in the adjuvant phase by 37% – a favorable trend for EFS – compared with the chemotherapy-placebo regimen (HR=0.63 [95% CI, 0.43-0.93]). The safety profiles of Keytruda and chemotherapy in Keynote-522 were consistent with previous studies.

“This innovative trial is the first to employ combined neoadjuvant and adjuvant treatment with Keytruda in patients with early-stage TNBC,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “The results of the Keynote-522 study, reported today, are very encouraging and have the potential to change the treatment of patients diagnosed with TNBC.”

“As an oncologist specializing in the treatment of TNBC, I am highly encouraged by the significant improvement in pCR rates with Keytruda plus chemotherapy in the neoadjuvant setting and the positive trend for event free-survival demonstrated in this trial,” said Dr. Peter Schmid, lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute. “There is significant need for new treatment regimens that can increase pCR rates in this patient population.”

As previously announced, Keytruda plus chemotherapy was granted Breakthrough Therapy designation (BTD) by the U.S. Food and Drug Administration (FDA) for the neoadjuvant treatment of patients with high-risk, early-stage TNBC. The BTD was granted based on data from Phase 1b KEYNOTE-173 and Phase 2 I-SPY2 trial, which demonstrated encouraging anti-tumor activity with neoadjuvant KEYTRUDA plus chemotherapy in these patients.

“These findings from the KEYNOTE-522 trial are exciting for the TNBC community – a community in particular need of scientific advances,” said Hayley Dinerman, executive director, Triple Negative Breast Cancer Foundation. “We are committed to supporting patients with TNBC, and we are pleased to see new data focused on earlier lines of treatment.”

As previously announced, Merck plans to share early interim analysis data from KEYNOTE-522 with regulatory authorities. The company continues to progress a robust clinical development program for KEYTRUDA in breast cancer, which encompasses several internal studies and external collaborative trials, including KEYNOTE-355 and KEYNOTE-242.