Merck Announces Two US Regulatory Milestones for KEYTRUDA® (pembrolizumab) in Triple-Negative Breast Cancer (TNBC)

FDA Grants Priority Review to Supplemental Biologics License Application (sBLA) for KEYTRUDA Plus Chemotherapy for the Treatment of Certain Patients With Metastatic TNBC Based on KEYNOTE-355 Trial

FDA Accepts sBLA for KEYTRUDA for the Treatment of Patients with High-Risk Early-Stage TNBC Based on KEYNOTE-522 Trial

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted two new supplemental Biologics License Applications (sBLAs) for KEYTRUDA, Merck’s anti-PD-1 therapy. The FDA has accepted and granted priority review for a new sBLA seeking accelerated approval for KEYTRUDA in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10), based on the Phase 3 KEYNOTE-355 trial. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of Nov. 28, 2020. The FDA also accepted for standard review a new sBLA for KEYTRUDA for the treatment of patients with high-risk early-stage TNBC, in combination with chemotherapy as neoadjuvant treatment, and then as a single agent as adjuvant treatment after surgery, based on the Phase 3 KEYNOTE-522 trial. The PDUFA date for this application is March 29, 2021.

“There is a real need to advance new treatment options for triple-negative breast cancer, an aggressive form of the disease. The FDA’s acceptance of these KEYTRUDA applications for review is an important step toward helping patients with both early-stage and metastatic disease,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “These acceptances mark the first U.S. applications for KEYTRUDA in breast cancer, and we look forward to working closely with the FDA to bring these new options to patients as quickly as possible.”

The applications are based on data from the KEYNOTE-355 and KEYNOTE-522 trials, respectively. In KEYNOTE-355, KEYTRUDA plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy alone in patients whose tumors expressed PD-L1 at CPS ≥10. Approximately 38% of patients enrolled in KEYNOTE-355 had tumors expressing PD-L1 at CPS ≥10. These data were presented at the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. As previously announced, the trial will continue without changes to evaluate the other dual primary endpoint of overall survival (OS).

In KEYNOTE-522 – the first randomized trial of an anti-PD-1 therapy in the neoadjuvant/adjuvant setting for TNBC – neoadjuvant KEYTRUDA plus chemotherapy resulted in a statistically significant increase in pathologic complete response (pCR) in patients with early-stage TNBC, regardless of PD-L1 expression. The KEYTRUDA regimen also demonstrated a favorable trend for the other dual primary endpoint of event-free survival (EFS). Data from the KEYNOTE-522 trial were presented at the European Society for Medical Oncology (ESMO) 2019 Congress and the 2019 San Antonio Breast Cancer Symposium (SABCS). As previously announced, KEYTRUDA plus chemotherapy was granted Breakthrough Therapy designation by the FDA for the neoadjuvant treatment of patients with high-risk early-stage TNBC.

About KEYNOTE-355

KEYNOTE-355 is a randomized, double-blinded, Phase 3 trial (ClinicalTrials.gov, NCT02819518) evaluating KEYTRUDA in combination with one of three different chemotherapies (investigator’s choice of nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) compared with placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent inoperable or metastatic TNBC. Patients were eligible to be enrolled in the trial if they had a disease-free interval of at least 6 months or were de novo metastatic. The dual primary endpoints are PFS and OS in patients whose tumors expressed PD-L1 (CPS ≥1 and CPS ≥10) and in all participants (intention-to-treat population). The secondary endpoints include objective response rate, duration of response, disease control rate and safety. The study enrolled 847 patients who were randomized 2:1 to receive KEYTRUDA (200 mg every three weeks) plus chemotherapy (investigator’s choice of nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) or placebo plus nab-paclitaxel, paclitaxel or gemcitabine/carboplatin.

About KEYNOTE-522

KEYNOTE-522 is a randomized, double-blind, Phase 3 trial (ClinicalTrials.gov, NCT03036488) evaluating KEYTRUDA in combination with chemotherapy compared with placebo plus chemotherapy as neoadjuvant therapy, followed by KEYTRUDA monotherapy compared with placebo as adjuvant therapy in patients with TNBC. The dual primary endpoints are pCR and EFS. The secondary endpoints include pCR rate using alternative definitions (i.e., no invasive or noninvasive residual cancer in breast or nodes) at the time of definitive surgery, OS, EFS in patients whose tumors express PD-L1 (CPS ≥1), safety and patient-reported outcomes. The study enrolled 1,174 patients who were randomized 2:1 to receive either:

• KEYTRUDA (every three weeks) plus paclitaxel (weekly) and carboplatin (weekly or every three weeks) for four cycles, followed by KEYTRUDA plus cyclophosphamide and either doxorubicin or epirubicin (every three weeks) for four cycles as neoadjuvant therapy prior to surgery, followed by nine cycles of KEYTRUDA (every three weeks) as adjuvant therapy post-surgery or;
• Placebo (every three weeks) plus paclitaxel (weekly) and carboplatin (weekly or every three weeks) for four cycles, followed by placebo plus cyclophosphamide and either doxorubicin or epirubicin (every three weeks) for four cycles, followed by nine cycles of placebo (every three weeks) as adjuvant therapy post-surgery.

About KEYTRUDA^® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.