KEYTRUDA is the first anti-PD-1/L1 therapy in combination with trastuzumab and chemotherapy to demonstrate a statistically significant improvement in OS in this patient population

Results from the final analysis of KEYNOTE-811 are being presented during a Proffered Paper Session at the European Society for Medical Oncology (ESMO) Congress 2024 and published simultaneously in the New England Journal of Medicine

In the U.S., KEYTRUDA, in combination with trastuzumab and chemotherapy, is indicated under accelerated approval for first-line treatment in the subset of this patient population whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1), based on prior KEYNOTE-811 results

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced overall survival (OS) results from the final analysis of the Phase 3 KEYNOTE-811 trial evaluating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. These data are being presented today during a proffered paper session at the European Society for Medical Oncology (ESMO) Congress 2024 (Presentation #1400O) and are also being simultaneously published in the New England Journal of Medicine.

After a median follow-up of 50.2 months (range, 31.1-64.4), the KEYTRUDA regimen demonstrated a statistically significant and clinically meaningful improvement in OS in the intention-to-treat (ITT) HER2-positive advanced gastric or GEJ study population, reducing the risk of death by 20% (HR=0.80 [95% CI, 0.67-0.94]; p=0.0040 [p-value bound 0.0201]) compared to trastuzumab and chemotherapy alone. For patients who received the KEYTRUDA regimen, median OS was 20.0 months (95% CI, 17.8-22.1) versus 16.8 months (95% CI, 14.9-18.7) for patients receiving trastuzumab plus chemotherapy alone.

The KEYTRUDA regimen also demonstrated a clinically meaningful improvement in OS in patients whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥1), reducing the risk of disease progression or death by 21% (HR=0.79 [95% CI, 0.66-0.95]) compared to trastuzumab and chemotherapy alone in these patients. Median OS was 20.1 months (95% CI, 17.9-22.9) for patients with tumors expressing PD-L1 (CPS ≥1) receiving the KEYTRUDA regimen versus 15.7 months (95% CI, 13.5-18.5) for patients receiving trastuzumab and chemotherapy alone. In the study, 85% of patients’ tumors expressed PD-L1 (CPS ≥1).

“The majority of patients with gastric and gastroesophageal cancer are diagnosed at an advanced stage, at which point the five-year survival rate is less than 10%,” said Dr. Yelena Y. Janjigian, chief attending physician, gastrointestinal oncology, Memorial Sloan Kettering Cancer Center, and global lead principal investigator for the KEYNOTE-811 trial. “These overall survival results from the KEYNOTE-811 trial are encouraging and show that adding pembrolizumab to trastuzumab and chemotherapy can extend the lives of certain patients with HER2-positive and PD-L1 positive gastric and gastroesophageal cancer.”

“With these new results, KEYNOTE-811 has met both of its primary endpoints, significantly improving progression-free and overall survival for patients with HER2-positive advanced gastric cancer, with the greatest benefit observed in patients whose tumors express PD-L1 (CPS ≥1),” said Dr. M. Catherine Pietanza, vice president, global clinical development, Merck Research Laboratories. “These new survival data add to the strong body of evidence supporting global approvals of this KEYTRUDA-based regimen and underscore the importance of providing promising new treatment options to patients.”

In the U.S., KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Since the FDA’s accelerated approval, the trial has met its dual primary endpoints of progression-free survival (PFS) and OS. These results have been shared with regulatory authorities worldwide.

In August 2023, the European Commission (EC) approved KEYTRUDA in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma in adults whose tumors express PD-L1 (CPS ≥1) based on PFS results from KEYNOTE-811.

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.

As announced, data spanning more than 20 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO Congress 2024.

Study design and additional data from KEYNOTE-811 KEYNOTE-811 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03615326) evaluating KEYTRUDA in combination with trastuzumab and chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. The dual primary endpoints are PFS per RECIST v1.1 as assessed by blinded independent central review and OS. Secondary endpoints include objective response rate (ORR), duration of response and safety. The trial enrolled 698 patients who were randomized to receive KEYTRUDA (200 mg every three weeks) in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy (investigator’s choice of 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin), or placebo in combination with trastuzumab and chemotherapy.

As previously announced, KEYNOTE-811 met the dual primary endpoint of PFS at an earlier interim analysis, results of which were presented at the ESMO Congress 2023. At this final analysis, in the ITT patient population, the PFS benefit observed in the previous interim analyses was maintained and the KEYTRUDA regimen reduced the risk of disease progression or death by 27% (HR=0.73 [95% CI, 0.61-0.87]), with a median PFS of 10.0 months (95% CI, 8.6-12.2) versus 8.1 months (95% CI, 7.0-8.5) for trastuzumab and chemotherapy alone. In patients with tumors expressing PD-L1 (CPS ≥1), the KEYTRUDA regimen reduced the risk of disease progression or death by 28% (HR=0.72 [95% CI, 0.60-0.87]), with a median PFS of 10.9 months (95% CI, 8.5-12.5) in the KEYTRUDA arm versus 7.3 months (95% CI, 6.8-8.4) for trastuzumab and chemotherapy alone. Based on a pre-specified subgroup analysis, the greatest benefit in PFS was observed in patients whose tumors express PD-L1 (CPS ≥1).

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Treatment related adverse events (TRAEs) occurred in 99% of patients receiving the KEYTRUDA regimen (n=350) and 100% of patients receiving trastuzumab and chemotherapy alone (n=346); Grade 3-4 TRAEs occurred in 58% (n=202) versus 50% (n=173), respectively; Grade 5 TRAEs occurred in 1.0% of patients receiving the KEYTRUDA regimen (n=4) versus 1.0% of patients receiving trastuzumab and chemotherapy alone (n=3). Treatment-related adverse events led to discontinuation of any study treatment in 37% of patients treated with the KEYTRUDA regimen (n=130) and 34% of patients treated with trastuzumab and chemotherapy alone (n=117).

Immune-mediated adverse events (AEs) and infusion reactions of any grade occurred in 40% of patients receiving the KEYTRUDA regimen (n=140) and 25% of patients receiving trastuzumab and chemotherapy alone (n=86); Grade 3-4 immune-mediated AEs and infusion reactions occurred in 11% (n=38) versus 3% (n=11), respectively; Grade 5 immune-mediated AEs and infusion reactions occurred in 1.0% of patients receiving the KEYTRUDA regimen (n=3) versus less than 1.0% of patients (n=1) who received trastuzumab and chemotherapy alone. The most common of these events (occurring in ≥10% of patients) were infusion reactions and hypothyroidism. Immune-mediated AEs and infusion reactions that led to discontinuation of any study treatment occurred in 8% of patients receiving the KEYTRUDA regimen (n=27) and 4% of patients receiving trastuzumab and chemotherapy alone (n=14).

About gastric cancer Gastric (stomach) cancer tends to develop slowly over many years and rarely causes early symptoms, resulting in most cases going undetected until an advanced stage.More than 70% of patients with gastric cancer develop advanced-stage disease. Most gastric cancers are adenocarcinomas (about 90-95%), 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 fifth leading cause of cancer death worldwide, with approximately 969,000 patients diagnosed and 660,000 deaths from the disease globally in 2022.In the U.S., it is estimated there will be approximately 26,890 patients diagnosed with gastric cancer and 10,880 deaths from the disease in 2024. The five-year survival rate for patients diagnosed with gastric cancer at an advanced stage is only 7%.

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 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 adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

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

KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

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 programmed death receptor-1 (PD-1) or the programmed death ligand 1 (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 (

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.