Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that KEYTRUDA, Merck’s anti-PD-1 therapy, has received two new approvals from the Japan Pharmaceuticals and Medical Devices Agency (PMDA). KEYTRUDA is approved for the treatment of patients with PD-L1-positive, hormone receptor-negative and human epidermal growth factor receptor 2 (HER2)-negative, inoperable or recurrent breast cancer, based on the results of the Phase 3 KEYNOTE-355 trial. Additionally, KEYTRUDA as a monotherapy is approved for the treatment of patients with unresectable, advanced or recurrent high microsatellite instability (MSI-H) colorectal cancer, based on results of the Phase 3 KEYNOTE-177 trial. With these approvals, KEYTRUDA has 15 authorized uses in Japan, including indications in nine tumor types as well as MSI-H tumors.

“We are pleased to offer two potential new treatment options with KEYTRUDA for patients in Japan based on compelling data from our clinical trial program,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “KEYTRUDA has now been approved across nine tumor types as well as MSI-H tumors in Japan, underscoring our commitment to advancing cancer care.”

“These approvals further demonstrate that KEYTRUDA and KEYTRUDA-based combinations have the potential to help certain patients in Japan who are facing cancers,” said Kyle Tattle, president, MSD Japan. “The prevalence of breast and colorectal cancer is particularly high in Japan, and we are committed to working with the government so that patients have access to these immunotherapy treatment options.”

KEYTRUDA Approved for the Treatment of Patients With PD-L1-Positive, Hormone Receptor-Negative and HER2-Negative, Inoperable or Recurrent Breast Cancer

The approval of KEYTRUDA for the treatment of patients with PD-L1-positive, hormone receptor-negative and HER2-negative, inoperable or recurrent breast cancer is based on results from the KEYNOTE-355 trial, in which KEYTRUDA in combination with chemotherapy – paclitaxel (pac), paclitaxel protein-bound (commonly known as nab-paclitaxel) or gemcitabine (gem) and carboplatin (carbo) – demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS) for patients with metastatic triple-negative breast cancer (TNBC) whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10). KEYTRUDA in combination with chemotherapy (pac, nab-paclitaxel or gem/carbo) reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.49, 0.86]; p=0.0012), with a median PFS of 9.7 months (95% CI, 7.6-11.3) versus 5.6 months (95% CI, 5.3-7.5), versus the same chemotherapy regimens alone in these patients. Overall survival results from KEYNOTE-355 will be presented at an upcoming medical meeting.

The Japanese package insert notes that in KEYNOTE-355, adverse reactions were observed in 212 patients (96.8%) out of the safety analysis set of 219 patients with positive PD-L1 (CPS≥10) (including 19 out of 19 Japanese patients) receiving KEYTRUDA at a dose of 200 mg every three weeks. The most common adverse reactions (≥20%) were anemia in 107 patients (48.9%), nausea in 90 patients (41.1%), neutropenia in 87 patients (39.7%), alopecia in 76 patients (34.7%), fatigue in 64 patients (29.2%), neutrophil count decreased in 52 patients (23.7%), diarrhea in 48 patients (21.9%), increased in 47 patients (21.5%) and vomiting in 44 patients (20.1%).

Triple-negative breast cancer is a type of breast cancer that tests negative for estrogen hormone receptors, progesterone hormone receptors and excess HER2 protein. It is an aggressive type of breast cancer that has a high risk for disease recurrence. Triple-negative breast cancer is known to be more prevalent in Japan than in the United States, as approximately 15% of patients with breast cancer in Japan are diagnosed with TNBC. Breast cancer is the most commonly diagnosed cancer in women in Japan, with more than 94,000 people diagnosed in 2020.

KEYTRUDA Approved for the Treatment of Patients With Unresectable, Advanced or Recurrent MSI-H Colorectal Cancer

The approval of KEYTRUDA as a monotherapy for the treatment of patients with unresectable, advanced or recurrent MSI-H colorectal cancer is based on results from the KEYNOTE-177 trial, in which KEYTRUDA significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0002) and doubled median PFS (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]) compared with chemotherapy agents, a current standard of care. The most common adverse reactions reported for KEYTRUDA in KEYNOTE-177 were consistent with that observed in previously reported studies of KEYTRUDA as a single agent.

Colorectal cancer starts in the colon or the rectum, and these cancers are referred to as colon cancer or rectal cancer depending on where the cancer starts. Colorectal cancer is the most commonly diagnosed cancer in Japan, and in 2020, it is estimated that there were nearly 157,000 cases of colorectal cancer diagnosed. MSI-H biomarkers are associated with many types of cancer, including colorectal cancer.