About KEYNOTE - 024

KEYNOTE-024 is a randomized, pivotal,phase 3 study (ClinicalTrials.gov, NCT02142738) evaluating pembrolizumabmonotherapy compared to standard of care(SOC) platinum-based chemotherapies in the treatment of patients with advanced NSCLC. Patients enrolled were those who had received no prior systemic chemotherapy treatment for their advanced disease and whose tumors expressed high levels of PD-L1 (defined as a tumor proportion score of 50 percent or more) as determined by a central laboratory using an immunohistochemistry assay. The study randomized 305 patients to receive pembrolizumab(200 mg every three weeks) or SOC platinum-based chemotherapies: paclitaxel+carboplatin, pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+carboplatin, or

gemcitabine+cisplatin. Pemetrexed maintenance therapy was permitted for patients with non-squamous histologies. In addition, patients randomized to the control had the option of crossing over to pembrolizumab upon disease progression. The primary endpointis PFS; secondary endpoints are OS and overall response rate (ORR).

About pembrolizumab injection 100 mg

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab 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.

Pembrolizumab is indicated for the treatment of patients with unresectable or metastatic melanoma.

Pembrolizumab is also indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 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 pembrolizumab. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Pembrolizumab is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.

Selected Important Safety Information for pembrolizumab

Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and occurred more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold pembrolizumab for Grade 2; permanently discontinue pembrolizumab for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold pembrolizumab for Grade 2 or 3; permanently discontinue pembrolizumab for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving pembrolizumab. 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 pembrolizumab. 

Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold pembrolizumab for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue pembrolizumab for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulinfor type 1 diabetes, and withhold pembrolizumab and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving pembrolizumab. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold pembrolizumabfor Grade 2; permanently discontinue pembrolizumab for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immunemediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold pembrolizumab and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume pembrolizumabwhen the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue pembrolizumab for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis. 

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue pembrolizumab.

Based on its mechanism of action, pembrolizumab can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of pembrolizumab.

Pembrolizumab was discontinued due to adverse reactions in 14% of 550 patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).

No formal pharmacokinetic drug interaction studies have been conducted withpembrolizumab.

It is not known whether pembrolizumab is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with pembrolizumab and for 4 months after the final dose.

Safety and effectiveness of pembrolizumab have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At MSD Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, MSD is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 270 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

About MSD

For 125 years, MSD has been a global health care leader working to help the world be well. MSD is a tradename of Merck & Co., Inc., Kenilworth, N.J., USA. Through our prescription medicines, vaccines, biologic therapies, and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.msd.com.

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