Merck (MRK) Announces Phase 3 KEYNOTE-522 Trial Met Dual Primary Endpoint of Event-Free Survival in Patients With High-Risk Early-Stage TNBC

May 13, 2021 6:46 AM EDT

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Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced positive results from the pivotal neoadjuvant/adjuvant Phase 3 KEYNOTE-522 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent (adjuvant) treatment after surgery. KEYNOTE-522 met its dual primary endpoint of event-free survival (EFS) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC). Based on an interim analysis conducted by the independent Data Monitoring Committee (DMC), neoadjuvant KEYTRUDA plus chemotherapy followed by adjuvant KEYTRUDA as monotherapy showed a statistically significant and clinically meaningful improvement in EFS compared with neoadjuvant chemotherapy alone. As previously communicated, KEYNOTE-522 met its other dual primary endpoint of pathological complete response (pCR). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified.

“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 Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “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. We are grateful to the study participants who are critical to our efforts to advance potential treatment options for patients with TNBC.”

An analysis of pCR from KEYNOTE-522 was presented at the European Society for Medical Oncology (ESMO) 2019 Congress and published in the New England Journal of Medicine. Findings showed a statistically significant increase in pCR for KEYTRUDA plus chemotherapy versus chemotherapy alone as neoadjuvant therapy in patients with early-stage TNBC, regardless of PD-L1 status. As previously announced, the company received a Complete Response Letter (CRL) from the FDA in March 2021 regarding Merck’s supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA for the treatment of patients with high-risk early-stage TNBC based on these pCR data and early interim EFS findings. The CRL followed the FDA’s Oncologic Drugs Advisory Committee meeting that voted 10-0 that a regulatory decision should be deferred until further data were available from KEYNOTE-522.

The KEYTRUDA clinical development program for TNBC encompasses several internal studies and external collaborative trials, including the ongoing studies KEYNOTE-242 and KEYNOTE-355.

Merck has an expansive clinical development program investigating KEYTRUDA in earlier lines of therapy including in neoadjuvant, adjuvant and locally advanced settings, with approximately 20 registrational studies ongoing.

About KEYNOTE-522

KEYNOTE-522 is a Phase 3, randomized, double-blind trial (, NCT03036488), evaluating a regimen of neoadjuvant KEYTRUDA in combination with chemotherapy followed by adjuvant KEYTRUDA as monotherapy versus a regimen of neoadjuvant chemotherapy followed by adjuvant placebo. 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, overall survival, EFS in patients whose tumors express PD-L1 (Combined Positive Score [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 as neoadjuvant therapy prior to surgery, followed by nine cycles of placebo (every three weeks) as adjuvant therapy post-surgery.

About Triple-Negative Breast Cancer (TNBC)

Triple-negative breast cancer is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Approximately 15-20% of patients with breast cancer are diagnosed with TNBC. TNBC tends to be more common in women who are younger than 40 years of age, who are African American or who have a BRCA1 mutation.

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 1,400 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.

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