Merck announced that the US Food and Drug Administration (FDA) approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2-directed Antibody Drug Conjugate (ADC), for the first-line treatment of adult patients with unresectable locally advanced or metastatic Triple-Negative Breast Cancer (TNBC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA-authorised test. These approvals represent the first PD-1 inhibitors plus Trop-2-directed ADC regimen in advanced TNBC.

These approvals are based on data from the phase 3 KEYNOTE-D19/ASCENT-04 trial demonstrating that KEYTRUDA plus Trodelvy reduced the risk of disease progression or death by 35 percent (HR=0.65 [95 percent CI, 0.51-0.84]; p=0.0009) versus KEYTRUDA plus chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin) for the first-line treatment of adult patients with PD-L1+ (CPS ≥10) unresectable locally advanced or metastatic TNBC.

KEYTRUDA plus Trodelvy resulted in a median Progression-Free Survival (PFS) of 11.2 months [95 percent CI, 9.3-16.7] versus 7.8 months [95 percent CI, 7.3-9.3] with KEYTRUDA plus chemotherapy. The Objective Response Rate (ORR) was higher with KEYTRUDA plus Trodelvy (61 percent [95 percent percent CI, 55-68]) than with KEYTRUDA plus chemotherapy (55 percent [95 percent CI, 48-62]), and complete responses occurred in 12 percent and 8 percent of patients, respectively. The effectiveness of KEYTRUDA QLEX for its approved indications has been established based upon evidence from the adequate and well-controlled studies conducted with KEYTRUDA and additional data from MK?3475A?D77 comparing the pharmacokinetic, efficacy and safety profiles of KEYTRUDA QLEX and KEYTRUDA.

Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology, Dana-Farber Cancer Institute, and a principal investigator of Merck’s KEYNOTE-D19 and Gilead’s ASCENT-04 study, said, “For people living with metastatic Triple-Negative Breast Cancer, the first treatment choice can be pivotal, as many patients may not have the opportunity to receive subsequent therapies. These approvals are heartening news for patients and the clinical community, and I believe offer practice-changing first-line treatment options.

Pembrolizumab (KEYTRUDA) in combination with sacituzumab govitecan-hziy (Trodelvy) is recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for breast cancer as a category 1 preferred first-line treatment option for certain patients with recurrent unresectable (local or regional) or stage IV (M1) TNBC whose tumors express PD-L1 (CPS ≥10).

Dr. Gursel Aktan, Vice President (VP), Global Clinical Development, Merck Research Laboratories, said, “Patients with PD-L1+ unresectable locally advanced or metastatic TNBC have limited treatment options in the first-line setting, as this aggressive disease often advances quickly. We now have new first-line treatment options that combine, for the first time, a PD-1 inhibitor with a Trop-2-directed ADC, and significantly reduce disease progression or death compared to KEYTRUDA plus chemotherapy. Today’s approvals of KEYTRUDA and KEYTRUDA QLEX each in combination with Trodelvy represent a meaningful milestone for those living with advanced TNBC.”

The median duration of exposure to KEYTRUDA was 8.5 months (range 1 day to 26.8 months).

Fatal adverse reactions occurred in 3.2 percent of patients receiving KEYTRUDA in combination with sacituzumab govitecan-hziy, including death due to unknown cause (0.9 percent), and completed suicide, neutropenic sepsis, sepsis, pneumonia and pulmonary embolism (0.5 percent each).

Serious adverse reactions occurred in 38 percent of patients receiving KEYTRUDA in combination with sacituzumab govitecan-hziy. Serious adverse reactions in ≥2 percent of patients were febrile neutropenia (7 percent), neutropenia (6 percent), diarrhea (5 percent), fatigue and pneumonia (2.3 percent each).

Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 9 percent of patients. The adverse reactions which resulted in permanent discontinuation of KEYTRUDA most commonly (≥1 percent) were pneumonitis and rash (1.4 percent each).

Dosage interruptions of KEYTRUDA due to adverse reactions occurred in 67 percent of patients. Adverse reactions which required dosage interruption in ≥2 percent of patients included neutropenia (36 percent), diarrhea (7 percent), upper respiratory tract infection (4.5 percent), anemia (4.1 percent), fatigue (4.1 percent), increased alanine aminotransferase (ALT) (3.2 percent), cough (2.7 percent), leukopenia (2.7 percent), nausea (2.7 percent), pyrexia (2.7 percent), rash (2.7 percent), vomiting (2.7 percent) and COVID-19 (2.3 percent).

The most common (≥25 percent) adverse reactions, including laboratory abnormalities, occurring in patients treated with KEYTRUDA in combination with sacituzumab govitecan-hziy were decreased neutrophil count and decreased hemoglobin (86 percent each), decreased leukocyte count (84 percent), diarrhea (72 percent), nausea (68 percent), decreased lymphocyte count (61 percent), fatigue (58 percent), alopecia (52 percent), increased alkaline phosphatase and increased glucose (50 percent each), increased ALT (47 percent), constipation (41 percent), increased aspartate aminotransferase (40 percent), rash (37 percent), decreased potassium (35 percent), increased lactate dehydrogenase (34 percent), vomiting (29 percent), abdominal pain, headache, and increased eosinophils (26 percent each) and decreased albumin (25 percent).

According to the NCCN Guidelines (Version 4.2026), category 1 is based upon high-level evidence (≥1 randomised phase 3 trials or high-quality, robust meta-analyses), there is uniform NCCN consensus (≥85 percent support of the panel) that the intervention is appropriate. Preferred intervention refers to interventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.