Merck’s Keytruda Receives FDA Priority Review for Two sBLAs in Triple-Negative Breast Cancer

Source | Jike Pharmaceutical News

On July 30, Merck Sharp & Dohme (MSD) announced that the U.S. FDA had accepted two new supplemental Biologics License Applications (sBLAs) for the anti-PD-1 monoclonal antibody Keytruda. One sBLA seeks 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). This application is based on positive results from the Phase 3 KEYNOTE-355 trial, has been granted Priority Review, and carries a PDUFA date of November 28, 2020. The other sBLA pertains to the use of Keytruda in combination with chemotherapy as neoadjuvant treatment for patients with high-risk early-stage TNBC, followed by single-agent Keytruda as adjuvant therapy after surgery. This application is based on the Phase 3 KEYNOTE-522 trial, is undergoing standard FDA review, and has a PDUFA date of March 29, 2021.

These two sBLA submissions are based on data from the KEYNOTE-355 and KEYNOTE-522 trials, respectively. In KEYNOTE-355, Keytruda in combination with chemotherapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared with chemotherapy alone in patients with PD-L1–expressing tumors with a Combined Positive Score (CPS) ≥10. Approximately 38% of patients enrolled in KEYNOTE-355 had PD-L1–expressing tumors with CPS ≥10. Detailed clinical data were presented in the online scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. As previously announced, the trial will continue without any changes to evaluate the other dual primary endpoint of overall survival (OS).

In KEYNOTE-522 (the first randomized trial of an anti-PD-1 agent for neoadjuvant/adjuvant treatment of triple-negative breast cancer [TNBC]), Keytruda in combination with chemotherapy met the primary endpoint of pathological complete response (pCR) as a neoadjuvant therapy for TNBC, regardless of PD-L1 expression levels. The Keytruda regimen also demonstrated a favorable trend in the other co-primary endpoint of event-free survival (EFS). Data from the KEYNOTE-522 trial were presented at the 2019 European Society for Medical Oncology (ESMO) Congress and the 2019 San Antonio Breast Cancer Symposium (SABCS). The use of Keytruda plus chemotherapy as neoadjuvant treatment for patients with high-risk early-stage TNBC has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA).

Triple-Negative Breast Cancer (TNBC) refers to a subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. It accounts for 10%–20% of all pathological types of breast cancer and predominantly affects premenopausal women. TNBC is the most aggressive form of breast cancer, exhibiting strong invasiveness, a high propensity for metastasis, and a very poor prognosis. The median survival time after diagnosis is typically no more than 20 months, and the 5-year survival rate is less than 15%.

“Triple-negative breast cancer requires new treatment options. The FDA’s acceptance of these two marketing applications for Keytruda is expected to benefit patients with early-stage and metastatic breast cancer,” said Dr. Roy Baynes, Chief Medical Officer, Senior Vice President, and Head of Global Clinical Development at Merck Sharp & Dohme AG. “This marks the first time that marketing applications for a breast cancer indication for Keytruda have been submitted in the United States. We look forward to working closely with the FDA to bring this new therapy to patients as soon as possible.”

Keytruda is an anti-PD-1 therapy that has received FDA approval for the treatment of more than 10 cancer indications, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), head and neck cancer, hepatocellular carcinoma, and renal cell carcinoma. Keytruda (pembrolizumab; brand name: Keytruda in China) has also been approved in China for the treatment of melanoma and non-small cell lung cancer.

References:

[1] Merck Announces Two US Regulatory Milestones for KEYTRUDA® (pembrolizumab) in Triple-Negative Breast Cancer (TNBC). Retrieved 2020-07-30, from https://investors.merck.com/news/press-release-details/2020/Merck-Announces-Two-US-Regulatory-Milestones-for-KEYTRUDA-pembrolizumab-in-Triple-Negative-Breast-Cancer-TNBC/default.aspx

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