RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced topline results from the Phase 3 KEYNOTE-585 trial, investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy as neoadjuvant treatment, followed by adjuvant treatment with KEYTRUDA plus chemotherapy, then KEYTRUDA monotherapy in patients with locally advanced resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma. At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, the study met one of its primary endpoints of pathological complete response (pCR) rate and demonstrated a statistically significant improvement in pCR rates compared with chemotherapy alone. For the primary endpoint of event-free survival (EFS), there was an improvement in the KEYTRUDA arm; however, results did not meet statistical significance per the pre-specified statistical analysis plan. The endpoint of overall survival (OS) was not formally tested since superiority was not reached for EFS. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting.

“While a statistically significant improvement in pathological complete response was observed in this study, we are disappointed that the KEYTRUDA regimen did not significantly improve event-free survival, a result that underscores the challenges in treating locally advanced resectable gastric cancer,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “Innovative research in earlier stages of cancer is critical to help patients achieve better outcomes, and our efforts continue in earnest. We are grateful to the patients and investigators for their participation in this study.”

Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers and is continuing to study KEYTRUDA for multiple uses in gastric, hepatobiliary, esophageal, pancreatic and colorectal cancers.

About KEYNOTE-585 KEYNOTE-585 is a randomized, double-blind, Phase 3 trial (ClinicalTrials.gov, NCT03221426) evaluating KEYTRUDA in combination with chemotherapy (cisplatin plus capecitabine or cisplatin plus 5-fluorouracil) as neoadjuvant treatment, followed by adjuvant treatment with KEYTRUDA plus chemotherapy, then KEYTRUDA monotherapy for the treatment of patients with locally advanced resectable gastric and GEJ adenocarcinoma. The primary endpoints included EFS, defined as the time from randomization to the first occurrence of either radiographic disease progression, a local/distant recurrence, clinical progression or death from any cause; pCR rate, defined as a lack of all signs of cancer in tissue samples; and OS, defined as the time from randomization to death from any cause. Secondary endpoints included disease-free survival and safety. The trial enrolled 1,007 patients who were randomized 1:1 to receive three cycles of KEYTRUDA (200 mg every three weeks) in combination with chemotherapy as neoadjuvant treatment, followed by adjuvant treatment with three cycles of KEYTRUDA (200 mg every three weeks) plus chemotherapy, then KEYTRUDA monotherapy (200 mg every three weeks for up to 11 cycles) or neoadjuvant placebo plus chemotherapy, followed by adjuvant placebo plus chemotherapy, then placebo alone.

About gastric cancer Gastric cancer – also called stomach cancer – is a type of cancer that begins in the stomach and tends to develop slowly over many years. Approximately 90-95% of gastric cancers are adenocarcinomas, which develop from cells in the innermost lining of the stomach (known as the mucosa). Gastric cancer is the fifth most diagnosed cancer and the fourth leading cause of cancer death worldwide, with approximately 1.1 million patients diagnosed and 768,000 patient deaths from the disease globally in 2020. In the U.S., it is estimated there will be approximately 26,500 patients diagnosed with gastric cancer and 11,000 patient deaths from the disease in 2023.

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 studying KEYTRUDA in earlier disease states, with approximately 20 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.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.Gastric Cancer KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA Severe and Fatal Immune-Mediated Adverse Reactions KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

Immune-Mediated Colitis KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (