Merck & Co., has announced that their flagship oncology drug, Keytruda (pembrolizumab), failed to show a survival benefit in triple-negative breast cancer (TNBC) patients in the Phase 3 KEYNOTE-119 study. However, the company is also running additional trials designed to enable Food and Drug Administration approval of the drug.
The news was released on 20 May 2019, after two months since the FDA gave accelerated approval to a rival, Roche’s Tecentriq.
The company announced that the Phase III KEYNOTE-119 study of Keytruda as a monotherapy in second- and third-line triple-negative breast cancer (TNBC) failed to extend overall survival in patients. The trial enrolled 622 patients, who were randomized to receive either Keytruda or one of four chemotherapy drugs used to treat TNBC.
“Metastatic triple-negative breast cancer is an aggressive and challenging disease to treat, especially after progression on initial standard-of-care treatment,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories in their press release.
“While we are disappointed by the outcome of this monotherapy trial, we are continuing to study KEYTRUDA in earlier stages of the disease and in combination with chemotherapy to address the unmet medical need of patients with triple negative breast cancer. We are grateful to the patients and investigators for their participation in this important study.”he said.
Merck said that because the overall survival primary endpoint was not met in KEYNOTE-119, other endpoints were not formally tested as per the trial’s protocol.
Keytruda is an immunotherapy drug known as a PD-1 checkpoint inhibitor that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. The humanized monoclonal antibody 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.
Works by a similar mechanism, Roche’s Tecentriq (atezolizumab), a PD-L1 checkpoint inhibitor was approved by FDA to be used in combination with Celgene’s chemotherapy drug Abraxane (nab-paclitaxel) for TNBC, in March 2019.
Abraxane is among the drugs being combined with Keytruda in the ongoing KEYNOTE-355 study.
The KEYTRUDA breast cancer clinical development program encompasses several internal and external collaborative studies, including registration-enabling studies in TNBC -KEYNOTE-355, KEYNOTE-242, and KEYNOTE-522.
TNBC 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 receptor, progesterone receptor or human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. As a result, TNBC does not respond to therapies targeting these markers, making it more difficult to treat. Approximately 10-20% of patients with breast cancer are diagnosed with TNBC according to the National Breast Cancer Foundation, Australia.