Findings Presented at the 57th American Society of Hematology Annual Meeting Demonstrate Activity of KEYTRUDA Therapy in Previously-Treated Multiple Myeloma Patients When Combined with Lena­lido­mide and Dexamethasone

Kenilworth, NJ (Press Release) – Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today new study findings investigating the use of KEYTRUDA® (pem­bro­lizu­mab), the com­pany’s anti-PD-1 ther­apy, in com­bi­na­tion with lena­lido­mide and low-dose dexa­meth­a­sone (two com­monly used treat­ments for multiple myeloma) in patients whose dis­ease has progressed after at least two lines of prior ther­apy, in­clud­ing a pro­te­a­some inhibitor and an IMiD (immune modulatory drug). The initial findings from the ongoing Phase 1 KEYNOTE-023 study showed an over­all response rate (ORR) of 76 per­cent (n=13/17), as assessed by the Inter­na­tional Myeloma Work­ing Group (IMWG) 2006 Criteria. These results will be presented today at the 57th American Society of Hematology (ASH) Annual Meeting by Jesus San Miguel, M.D., Ph.D., Clínica Universidad de Navarra, Pamplona, Spain (Abstract #505). Based in part on these data, Merck has ini­ti­ated two Phase 3 studies eval­u­ating KEYTRUDA in the treat­ment of multiple myeloma.

“Many patients with multiple myeloma relapse after their initial treat­ment, reinforcing the need for addi­tional treat­ment options,” said Dr. Jesus San Miguel. “These findings highlight the poten­tial of combining KEY­TRUDA with an IMiD and dexa­meth­a­sone in patients who have multiple myeloma.”

“Our clin­i­cal pro­gram explores the poten­tial for KEYTRUDA across broad patient pop­u­la­tions, in­clud­ing in com­bi­na­tion with other med­i­cines,” said Roger Dansey, M.D., senior vice pres­i­dent and thera­peutic area head, on­col­ogy late-stage devel­op­ment, Merck Research Laboratories. “We are en­cour­aged by these results, showing responses in patients who have re­lapsed fol­low­ing treat­ment for multiple myeloma when treated with KEYTRUDA in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, and look for­ward to build­ing on these data.”

Results from KEYNOTE-023 Presented at ASH

In the study with 50 heavily pre-treated patients, initial findings from 17 patients who were treated with KEY­TRUDA (pem­bro­lizu­mab) in com­bi­na­tion with lena­lido­mide and low-dose dexa­meth­a­sone dem­onstrated an ORR of 76 per­cent (n=13/17) (per IMWG 2006), in­clud­ing four very good partial responses (24%) and nine partial responses (53%).

Adverse events in all 50 patients were con­sis­tent with pre­vi­ously reported safety data for KEYTRUDA as well as lena­lido­mide and low-dose dexa­meth­a­sone. Grade 3 or 4 treat­ment-related adverse events in­cluded: neu­tro­penia (n=11), thrombo­cytopenia (n=4), diarrhea (n=1), fatigue (n=1), anemia (n=4), hyper­glycemia (n=3) and muscle spasms (n=1). Immune-mediated adverse events in­cluded: adrenal insufficiency (n=1), hyper­thyroidism (n=2), hypo­thyroidism (n=2), and thyroiditis (n=1). No treat­ment-related deaths were re­ported.

About the KEYTRUDA Development Program and KEYNOTE-023

Merck is conducting a broad hema­to­logical malig­nan­cy pro­gram with approx­i­mately 20 clin­i­cal trials, in­clud­ing four registration-enabling studies and more than 15 com­bi­na­tions across a variety of lym­phomas, myeloma, leukemia, and other hema­to­logic malig­nan­cies. Registration-enabling trials of KEYTRUDA are cur­rently enrolling patients in mel­anoma, NSCLC, head and neck cancer, bladder cancer, gastric cancer, colo­rectal cancer, esophageal cancer, breast cancer, Hodgkin lym­phoma, multiple myeloma and other tumors, with further trials in planning for other cancers.

KEYNOTE-023 is a global, open-label, Phase 1 study designed to eval­u­ate KEYTRUDA treat­ment in combi­na­tion with dexa­meth­a­sone and two dif­fer­en­t doses of lena­lido­mide in approx­i­mately 75 patients with re­lapsed/​refractory multiple myeloma (RRMM). Patients will receive KEYTRUDA (2 mg/kg every two weeks) in combi­na­tion with lena­lido­mide (10 mg or 25 mg) or KEYTRUDA (200 mg fixed dose every two weeks) with lena­lido­mide (10 mg or 25 mg); all patients will receive 40 mg low-dose dexa­meth­a­sone weekly. Primary end­points in­clude safety and tolerability; sec­ond­ary end­points in­clude ORR, duration of response, pro­gres­sion-free survival (PFS), and over­all survival (OS).

About Multiple Myeloma

Multiple myeloma is a cancer of blood plasma cells in which ab­nor­mal plasma cells multiply un­con­trol­lably in the bone marrow and occasionally in other parts of the body. Manifestations of the dis­ease often in­clude bone pain and fractures, and may in­clude kidney problems, a weakened immune sys­tem weakness, and confusion. Multiple myeloma is the second most common blood cancer. In 2015, an esti­mated 26,850 people are ex­pec­ted to be diag­nosed and an esti­mated 11,240 people are ex­pec­ted to die of the dis­ease in the U.S. alone.

About KEYTRUDA® (pem­bro­lizu­mab) Injection 100 mg

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

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg admin­istered as an in­tra­venous in­fusion over 30 min­utes every three weeks 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 KEYTRUDA. KEYTRUDA is also indicated at the same dosing for the treat­ment of patients with unresectable or metastatic mel­anoma and dis­ease pro­gres­sion fol­low­ing ipilimumab and, if BRAF V600 mutation pos­i­tive, a BRAF inhibitor. These indi­ca­tions are 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 these indi­ca­tions may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in the con­firmatory trials.

Selected Important Safety Information for KEYTRUDA® (pem­bro­lizu­mab)

Pneumonitis, in­clud­ing fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 12 (2.9%) of 411 mel­anoma patients, in­clud­ing Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, re­spec­tive­ly, receiving KEYTRUDA. Pneumonitis occurred in 19 (3.5%) of 550 patients with NSCLC, in­clud­ing Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneu­mo­nitis in patients, receiving KEYTRUDA. 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.

Colitis (in­clud­ing microscopic colitis) occurred in 4 (1%) of 411 patients with mel­anoma, in­clud­ing Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, re­spec­tive­ly, receiving KEYTRUDA. Colitis occurred in 4 (0.7 %) of 550 patients with NSCLC, in­clud­ing Grade 2 (0.2%) or 3 (0.4%) colitis in patients receiving KEYTRUDA. 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.

Hepatitis occurred in patients receiving KEYTRUDA. Hepatitis (in­clud­ing auto­immune hepatitis) occurred in 2 (0.5%) of 411 patients with mel­anoma, in­clud­ing a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. 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.

Hypophysitis occurred in 2 (0.5%) of 411 patients with mel­anoma, in­clud­ing a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Hypo­physitis occurred in 1 (0.2 %) of 550 patients with NSCLC, 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 indicated. Withhold KEYTRUDA for Grade 2 and withhold or dis­con­tinue for Grade 3 or Grade 4 hypo­physitis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients with mel­anoma, in­clud­ing Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, re­spec­tive­ly, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients with mel­anoma, in­clud­ing a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Hyper­thyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, in­clud­ing Grade 2 (0.7%) or 3 (0.3%). Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, in­clud­ing Grade 2 (5.5%) or 3 (0.2%). 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 KEYTRUDA for Grade 3 or Grade 4 hyper­thyroidism.

Type 1 diabetes mellitus, in­clud­ing diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyper­glycemia or other signs and symp­toms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and admin­ister anti-hyperglycemics in patients with severe hyper­glycemia.

Nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 3 (0.7%) patients with mel­anoma, con­sist­ing of one case of Grade 2 auto­immune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; perma­nently dis­con­tinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clin­i­cally im­por­tant immune-mediated adverse reac­tions can occur. For sus­pected immune-mediated adverse reac­tions, ensure adequate evaluation to con­firm etiology or exclude other causes. Based on the severity of the adverse reac­tion, withhold KEYTRUDA and admin­ister corticosteroids. Upon im­prove­ment of the adverse reac­tion to Grade 1 or less, ini­ti­ate corticosteroid taper and con­tinue to taper over at least 1 month. Resume KEYTRUDA when the adverse reac­tion remains at Grade 1 or less fol­low­ing steroid taper. Permanently dis­con­tinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reac­tion that recurs and for any life-threatening immune-mediated adverse reac­tion.

Across clin­i­cal studies with KEYTRUDA, the fol­low­ing clin­i­cally sig­nif­i­cant, immune-mediated adverse reac­tions have occurred: bullous pemphigoid and Guillain-Barré syn­drome. The fol­low­ing clin­i­cally sig­nif­i­cant, immune-mediated adverse reac­tions occurred in less than 1% of patients with mel­anoma treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The fol­low­ing clin­i­cally sig­nif­i­cant, immune-mediated adverse reac­tions occurred in less than 1% of 550 patients with NSCLC treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

Infusion-related reac­tions, in­clud­ing severe and life-threatening reac­tions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symp­toms of in­fusion related reac­tions in­clud­ing rigors, chills, wheezing, pruritus, flushing, rash, hypo­­tension, hypoxemia, and fever. For severe or life-threatening reac­tions, stop in­fusion and perma­nently dis­con­tinue KEYTRUDA.

Based on its mech­a­nism of action, KEYTRUDA 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 KEYTRUDA.

Among the 411 patients with metastatic mel­anoma, KEYTRUDA was dis­con­tinued for adverse reac­tions in 9% of 411 patients. Adverse reac­tions, reported in at least two patients that led to dis­con­tinu­a­tion of KEYTRUDA were: pneu­mo­nitis, renal failure, and pain. Serious adverse reac­tions occurred in 36% of patients. The most frequent serious adverse reac­tions, reported in 2% or more of patients, were renal failure, dyspnea, pneu­monia, and cellulitis. The most common adverse reac­tions (reported in at least 20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), de­creased appetite (26%), con­sti­pa­tion (21%), arthralgia (20%), and diarrhea (20%).

Among the 550 patients with metastatic NSCLC, KEYTRUDA was dis­continued due to adverse reac­tions in 14% of patients. Serious adverse reac­tions occurred in 38% of patients. The most frequent serious adverse reac­tions reported in 2% or more 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%), de­creased appetite (25%), dyspnea (23%), and cough (29%).

No formal phar­ma­co­ki­netic drug inter­action studies have been conducted with KEYTRUDA.

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

Safety and effectiveness of KEYTRUDA 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 Merck 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. For more in­­for­ma­tion about our on­col­ogy clin­i­cal trials, visit www.merck.com/clinicaltrials.

About Merck

Today's Merck is a global health care leader work­ing to help the world be well. Merck is known as MSD outside the United States and Canada. 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 health care through far-reaching policies, pro­grams and part­ner­ships. For more in­­for­ma­tion, visit www.merck.com and connect with us on Twitter, Facebook, YouTube and LinkedIn.

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Please see Prescribing Information for KEYTRUDA (pem­bro­lizu­mab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and the Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

Source: Merck.