August 29, 2024 6:30 am ET--RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today provided updates on two Phase 3 trials, KEYNOTE-867 and KEYNOTE-630. Merck is discontinuing the Phase 3 KEYNOTE-867 trial evaluating KEYTRUDA ® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with stereotactic body radiotherapy (SBRT) for the treatment of patients with stage I or II (stage IIB N0, M0) non-small cell lung cancer (NSCLC), including those who are medically inoperable or have refused surgery. This decision is based on the recommendation of an independent Data Monitoring Committee (DMC), which reviewed data from a planned interim analysis. At the pre-specified interim analysis, KEYTRUDA in combination with SBRT did not demonstrate an improvement in event-free survival (EFS) or overall survival (OS), the study’s primary endpoint and key secondary endpoint, respectively, compared to placebo plus SBRT, and the benefit/risk profile of the combination did not support continuing the trial. KEYTRUDA in combination with SBRT was associated with higher rates of adverse events (AEs), including AEs leading to death, compared with SBRT and placebo.
Merck is also discontinuing the Phase 3 KEYNOTE-630 trial evaluating KEYTRUDA for the adjuvant treatment of patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) following surgery and radiation, based on the recommendation of an independent DMC. The DMC recommended that the study should be stopped for futility as the risk/benefit profile did not support continuing the trial. Data from a pre-planned analysis showed that KEYTRUDA did not cross the boundary for statistical significance in recurrence-free survival (RFS), the study’s primary endpoint. The study’s key secondary endpoint, OS, was not formally tested, but at the time of the analysis, the results did not favor KEYTRUDA compared to placebo. The safety profile of KEYTRUDA in this trial was consistent with the established safety profile of KEYTRUDA.
Merck has informed study investigators and advises patients in the studies to speak to their study team and physician regarding next steps and treatment options. Data analyses for KEYNOTE-867 and KEYNOTE-630 are ongoing, and the results will be shared with the scientific community and regulatory agencies.
“Our understanding of cancer and how it can be treated has rapidly evolved in recent years, but unmet needs remain across different types of cancer and stages of disease,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “That is why we continue our rigorous exploration of innovative treatment approaches in cancers with high unmet need, such as non-small cell lung cancer and cutaneous squamous cell carcinoma, with the goal to help even more patients. We are extremely grateful to all of the patients, caregivers and investigators for their participation in these studies.”
About KEYNOTE-867
KEYNOTE-867 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03924869 ) evaluating KEYTRUDA plus SBRT compared to placebo plus SBRT for the treatment of adult patients with unresected stage I or II (stage IIB N0, M0) NSCLC. Patients in KEYNOTE-867 were medically inoperable, which included patients who could not undergo thoracic surgery due to existing medical illness(es) or anatomically unresectable tumor, or who decided to treat with SBRT as definitive therapy rather than surgery, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. The primary endpoint is EFS, and key secondary endpoints include OS and safety. EFS is defined as the time from randomization to the first occurrence of local, regional, or distant recurrence of disease, or death due to any cause. The trial enrolled an estimated 436 patients who were randomized 1:1 to receive either:
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KEYTRUDA (200 mg) every three weeks (Q3W) for up to 17 cycles (up to approximately one year) plus SBRT once every three days for three, four, five or eight fractions (dependent on tumor type/location; 45-70 Gray total) over approximately two weeks; or
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Placebo Q3W for up to 17 cycles (up to approximately one year) plus SBRT once every three days for three, four, five or eight fractions (dependent on tumor type/location; 45-70 Gray total) over approximately two weeks.
About KEYNOTE-630
KEYNOTE-630 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03833167 ) evaluating KEYTRUDA as adjuvant therapy in patients with high-risk locally advanced cSCC who have undergone surgery with or without positive margins and completed adjuvant radiotherapy compared to placebo. The primary endpoint is RFS, and key secondary endpoints include OS and safety. The trial enrolled an estimated 430 patients who were randomized to receive either:
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KEYTRUDA (400 mg intravenously [IV] every six weeks [Q6W] for up to nine cycles) as adjuvant therapy following surgery and radiation; or
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Placebo (IV Q6W for up to nine cycles) as adjuvant therapy following surgery and radiation.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.48 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.
About cutaneous squamous cell carcinoma
Cutaneous squamous cell carcinoma is the second most common non-melanoma skin cancer and forms in squamous cells, which are in the outer part of the epidermis. This type of skin cancer is usually caused by prolonged exposure to ultraviolet (UV) radiation, either from the sun or from artificial sources, such as tanning beds. Cutaneous squamous cell carcinoma is five times more prevalent than melanoma, and prevalence has been increasing for many years, likely due to better skin cancer detection, more sun exposure and people living longer. In the U.S., an estimated 1.8 million cases of cSCC are diagnosed each year, accounting for approximately 20% of all skin cancer cases.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer.
About KEYTRUDA ® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that 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.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn .