KENILWORTH, N.J.--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded label for KEYTRUDA, Merck?s anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (tumor proportion score [TPS] =1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. The approval is based on results from the Phase 3 KEYNOTE-042 trial, in which overall survival (OS) was sequentially tested as part of a pre-specified analysis plan. In the trial, KEYTRUDA monotherapy demonstrated a statistically significant improvement in OS compared with chemotherapy alone in patients whose tumors expressed PD-L1 with a TPS =50%, with a TPS =20%, and then in the entire study population (TPS =1%). ?This expanded first-line indication now makes KEYTRUDA monotherapy an option for more patients with non-small cell lung cancer, including those for whom combination therapy may not be appropriate,? said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see ?Selected Important Safety Information? below. ?The KEYNOTE-042 trial demonstrated a survival benefit with KEYTRUDA monotherapy across histologies in certain patients with stage III or metastatic non-small cell lung cancer whose tumors expressed PD-L1 in at least 1% of tumor cells,? said Dr. Gilberto Lopes, associate director for global oncology at the Sylvester Comprehensive Cancer Center at the University of Miami. ?As a practicing oncologist, having additional options available for patients is important in the rapidly evolving treatment landscape for lung cancer, which remains the leading cause of cancer death in the United States.? KEYTRUDA was the first anti-PD-1 therapy in metastatic NSCLC approved in the first-line setting as combination therapy or monotherapy. About KEYNOTE-042 The approval was based on data from the KEYNOTE-042 trial, a randomized, multi-center, open-label, active-controlled trial in patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors expressed PD-L1 (TPS =1%) and who had not received prior systemic treatment for metastatic NSCLC. Patients with EGFR or ALK genomic tumor aberrations; autoimmune disease that required systemic therapy within two years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of radiation in the thoracic region within 26 weeks prior to initiation of study treatment were ineligible. The study enrolled 1,274 patients who were randomized (1:1) to receive KEYTRUDA 200 mg intravenously every three weeks (n=637) or investigator?s choice of either of the following chemotherapy regimens (n=637):

• Pemetrexed 500 mg/m²?every three weeks and carboplatin AUC 5 to 6 mg/mL/min every three weeks on Day 1 for a maximum of six cycles followed by optional pemetrexed 500 mg/m²?every three weeks for patients with nonsquamous histologies; or
• Paclitaxel 200 mg/m²?every three weeks and carboplatin AUC 5 to 6 mg/mL/min every three weeks on Day 1 for a maximum of six cycles followed by optional pemetrexed 500 mg/m²?every three weeks for patients with nonsquamous histologies

Treatment with KEYTRUDA continued until RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined progression of disease, unacceptable toxicity, or a maximum of 24 months. The main efficacy outcome measure was OS in the subgroup of patients with TPS =50% NSCLC, the subgroup of patients with TPS =20% NSCLC, and the overall population with TPS =1% NSCLC. Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) in the subgroup of patients with TPS =50% NSCLC, the subgroup of patients with TPS =20% NSCLC, and the overall population with TPS =1% NSCLC as assessed by a blinded independent central radiologists? (BICR) review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. Efficacy Results from KEYNOTE-042 * Based on the stratified Cox proportional hazard model ^??Based on a stratified log-rank test; compared to a p-Value boundary of 0.0291 ^??Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints ? Not significant compared to a p-Value boundary of 0.0291 ^??Based on observed duration of response The results of all efficacy outcome measures in the subgroup of patients with PD-L1 TPS =20% NSCLC were intermediate between the results of those with PD-L1 TPS =1% and those with PD-L1 TPS =50%. In a pre-specified exploratory subgroup analysis for patients with TPS 1-49% NSCLC, the median OS was 13.4 months (95% CI, 10.7-18.2) for the KEYTRUDA group and 12.1 months (95% CI, 11.0-14.0) in the chemotherapy group, with an HR of 0.92 (95% CI, 0.77-1.11). In KEYNOTE-042, the safety of KEYTRUDA was investigated in patients with PD-L1 expressing, previously untreated stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC. KEYTRUDA was discontinued for adverse reactions in 19% of 636 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3.0%), death due to unknown cause (1.6%), and pneumonia (1.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 33% of patients; the most common adverse reactions or laboratory abnormalities leading to interruption of KEYTRUDA (=2%) were pneumonitis (3.1%), pneumonia (3.0%), hypothyroidism (2.2%), and increased ALT (2.0%). The most frequent (=2%) serious adverse reactions were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (=20%) with KEYTRUDA was fatigue (25%). About KEYTRUDA?^??(pembrolizumab) Injection, 100mg KEYTRUDA is an anti-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 950 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. KEYTRUDA?^??(pembrolizumab) Indications and Dosing Melanoma KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence. Lung Cancer KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC. KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 [tumor proportion score (TPS) =1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS =1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. In NSCLC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, as appropriate. Head and Neck Cancer KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. 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. In HNSCC, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Classical Hodgkin Lymphoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. 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. In adults with cHL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Primary Mediastinal Large B-Cell Lymphoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. 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 confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy. In adults with PMBCL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Urothelial Carcinoma KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) =10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. In locally advanced or metastatic urothelial carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Microsatellite Instability-High (MSI-H) Cancer KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

• solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
• colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

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. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established. In adult patients with MSI-H cancer, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Gastric Cancer KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS =1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. 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. The recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Cervical Cancer KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy 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 for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity or up to 24 months in patients without disease progression. Hepatocellular Carcinoma KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 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. The recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Merkel Cell Carcinoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. 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. The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Selected Important Safety Information for KEYTRUDA Immune-Mediated Pneumonitis KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis. Immune-Mediated Colitis KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis. Immune-Mediated Hepatitis KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA. Immune-Mediated Endocrinopathies KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in patients with HNSCC, occurring in 15% (28/192) of patients. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia. Immune-Mediated Nephritis and Renal Dysfunction KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis. Immune-Mediated Skin Reactions Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the sever