FDA Will Review Two New Applications Seeking Keytruda Approval for TNBC

by Fitcoachion | Last Updated: August 10, 2020



Keytruda, TNBC

The U.S. Food and Drug Administration (FDA) has accepted to review two new Merck applications requesting the approval of Keytruda (pembrolizumab) for the treatment of patients with different forms of triple-negative breast cancer (TNBC).

One of the two supplemental biologics license applications (sBLAs) was granted priority review, which speeds FDA action, with a Prescription Drug User Fee Act (

That means the U.S. regulatory agency will make a decision by that date on whether to approve Keytruda, in combination with chemotherapy, as a treatment for TNBC. Specifically, the combo therapy would be used in this indication to treat people with inoperable (locally recurrent unresectable) or metastatic TNBC, whose tumors have at least 10% of cells producing the PD-L1 protein.

The second sBLA, which was accepted for standard review, is requesting the approval of a neoadjuvant regimen of Keytruda and chemotherapy for the treatment of people with high-risk, early-stage TNBC. Neoadjuvant treatments aim to shrink a tumor before patients undergo surgery. Following the cancer’s surgical removal, these patients would then receive Keytruda alone as an adjuvant therapy — a treatment that seeks to prevent the cancer from returning. For this sBLA, the FDA set a PDUFA action date for March 29, 2021.

“There is a real need to advance new treatment options for triple-negative breast cancer, an aggressive form of the disease,” Roy Baynes, senior vice president, head of global clinical development, and chief medical officer for Merck Research Laboratories, said in a press release.

“The FDA’s acceptance of these Keytruda applications for review is an important step toward helping patients with both early-stage and metastatic disease,” Baynes said. “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.”

Keytruda is an immune checkpoint inhibitor developed by Merck (known as MSD outside the U.S. and Canada) that has been approved both in the U.S. and Europe for the treatment of different types of cancer.

It works by preventing PD-1, a protein receptor found on the surface of immune cells, from interacting with its signaling molecules, or ligands, called PD-L1 and PD-L2, which are produced by cancer cells. This allows immune cells to recognize and eliminate cancer cells more effectively.

The first sBLA was supported by data from the Phase 3 KEYNOTE-355 trial (NCT02819518), involving 847 people with advanced TNBC whose tumors contain PD-L1. That trial is currently investigating the safety and efficacy of Keytruda in combination with one of three chemotherapy agents of choice: Abraxane (nab-paclitaxel), Taxol (paclitaxel) or Gemzar/Paraplatin (gemcitabine/carboplatin).

Data from KEYNOTE-355, presented at the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that, compared with chemo alone, the combination therapy significantly prolonged the time patients lived without disease progression (median of 5.6 vs. 9.7 months) in the subset of participants whose tumors had at least 10% of cells producing the PD-L1 protein.

Follow-up is still ongoing to assess the effects of the combination therapy on the participants’ overall survival, the second major endpoint of the study.

The second sBLA was supported by data from the Phase 3 KEYNOTE-522 trial (NCT03036488), the first study to investigate the effects of an anti-PD-1 therapy in a neoadjuvant and adjuvant setting in 1,174 patients with early TNBC.

Compared with chemo alone, the combination of Keytruda and chemotherapy given before surgery increased the percentage of people with early-stage TNBC who showed no signs of cancer in tissue samples collected after their surgery, demonstrating what scientists call a pathological complete response. That data from KEYNOTE-522, presented by the company in previous meetings, was true for all patients, regardless of the levels of PD-L1 found in their tumors.

When given in a neoadjuvant setting, Keytruda also seemed to prolong the time patients lived until showing signs of disease progression before surgery, having their cancer return, or dying to any cause (event-free survival).

The FDA had previously awarded breakthrough therapy designation to the combination therapy of Keytruda and chemotherapy as a neoadjuvant treatment for those with high-risk, early-stage TNBC.

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