Merck Announces Phase 3 KEYNOTE-756 Trial Met Primary Endpoint of Pathological Complete Response (pCR) Rate in Patients With High-Risk, Early-Stage ER+/HER2- Breast Cancer
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the pivotal Phase 3 KEYNOTE-756 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy met one of its dual primary endpoints of pathological complete response (pCR) rate following the neoadjuvant part of the neoadjuvant/adjuvant study regimen in patients with high-risk, early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. At a prespecified interim analysis conducted by an independent Data Monitoring Committee (DMC), the KEYTRUDA-based regimen demonstrated a statistically significant improvement in pCR rate compared to neoadjuvant placebo plus chemotherapy. A pCR is defined as a lack of all signs of cancer in tissue samples analyzed following completion of neoadjuvant therapy and definitive surgery.
Based on the recommendation of the DMC, the trial will continue without changes to evaluate the other dual primary endpoint of event-free survival (EFS), per the trial design. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting.
“This is the first positive Phase 3 study evaluating an immunotherapy-based regimen for patients with high-risk, early-stage ER-positive, HER2-negative breast cancer, and an important milestone in our efforts to advance research in early-stage breast cancer,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “We look forward to sharing the detailed results with the medical community and thank the patients and investigators for their important contributions to this study.”
“While significant advancements have been made in the treatment of ER-positive, HER2-negative breast cancer, people diagnosed with high-risk disease as assessed by clinical and pathologic criteria typically have a worse prognosis and limited options before surgery,” said Dr. Fatima Cardoso, director of the Breast Unit of the Champalimaud Clinical Centre, Lisbon, Portugal and co-principal investigator. “Data from KEYNOTE-756 suggest that adding pembrolizumab to neoadjuvant chemotherapy before surgery can significantly improve the pCR rate compared to neoadjuvant chemotherapy alone for people with high-risk, early-stage ER-positive, HER2-negative breast cancer.”
“Worldwide, more than two million people are diagnosed with breast cancer each year, and it is critically important that breast cancer is found and treated early, especially for patients with high-risk disease,” said Dr. Aditya Bardia, attending physician, medical oncology, Massachusetts General Hospital, director, breast cancer research, Massachusetts General Cancer Center, Associate professor, Harvard Medical School and co-principal investigator. “While we wait for event-free survival data, these initial pCR results provide a potentially encouraging signal and may have important therapeutic implications for patients with high-risk, early-stage ER-positive, HER2-negative breast cancer.”
In the U.S., KEYTRUDA is approved for two indications for the treatment of patients with triple-negative breast cancer (TNBC). Based on results from KEYNOTE-522, KEYTRUDA is approved in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery for patients with high-risk, early-stage TNBC. Based on results from KEYNOTE-355, KEYTRUDA is approved in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (combined positive score [CPS ≥10]) as determined by an FDA-approved test. In addition to the U.S., KEYNOTE-522 and KEYNOTE-355 supported the approvals of KEYTRUDA-based regimens for certain patients with high-risk early-stage TNBC and locally recurrent unresectable metastatic TNBC, respectively, in more than 90 countries around the world.