Kenilworth, NJ (Press Release) – Merck (NYSE:MRK), known as MSD outside the United States and Canada, today provided an update on two com­bi­na­tion studies of KEYTRUDA® (pem­bro­lizu­mab), the com­pany’s anti-PD-1 ther­apy, in the blood cancer multiple myeloma. Merck has accepted the external Data Monitoring Committee recom­men­da­tion to pause new enrollment on KEYNOTE-183 and KEYNOTE-185, two studies exploring KEYTRUDA treat­ment in com­bi­na­tion with other ther­a­pies in multiple myeloma. The pause is to allow for addi­tional in­­for­ma­tion to be collected to better under­stand more reports of death in the KEYTRUDA groups. Patients cur­rently enrolled in these two studies will con­tinue to receive treat­ment. Other studies of KEYTRUDA con­tinue unchanged.

KEYNOTE-183 is a Phase 3 study com­par­ing poma­lido­mide and low-dose dexa­meth­a­sone with KEYTRUDA to poma­lido­mide and low-dose dexa­meth­a­sone alone in patients with refractory or re­lapsed and refractory multiple myeloma (rrMM) who have undergone at least 2 lines of prior treat­ment. KEYNOTE-185 is a Phase 3 study com­par­ing lena­lido­mide and low-dose dexa­meth­a­sone with KEYTRUDA to lena­lido­mide and low-dose dexa­meth­a­sone alone in patients with newly diag­nosed and treat­ment-naïve multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant (Auto-SCT).

KEYTRUDA® (pem­bro­lizu­mab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treat­ment of patients with unresectable or metastatic mel­anoma at a fixed dose of 200 mg every three weeks until disease pro­gres­sion or unacceptable toxicity.

Lung Cancer

KEYTRUDA (pem­bro­lizu­mab), as a single agent, is indicated for the first-line treat­ment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 ex­pres­sion [tumor pro­portion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also 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.

KEYTRUDA, in com­bi­na­tion with pemetrexed and carboplatin, is indicated for the first-line treat­ment of patients with metastatic non­squamous NSCLC. This indi­ca­tion is approved under accel­er­ated approval based on tumor response rate and pro­gres­sion-free survival. Continued approval for this in­dica­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in the con­firmatory trials.

In metastatic NSCLC, KEYTRUDA (pem­bro­lizu­mab) is admin­istered at a fixed dose of 200 mg 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 pemetrexed and carboplatin.

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 is admin­istered at a fixed dose of 200 mg 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 three 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 (pem­bro­lizu­mab) is admin­istered at a fixed dose of 200 mg 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 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 who are not eli­gible for cisplatin-containing chemo­ther­apy. 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 also indicated for the treat­ment of patients with locally ad­vanced or metastatic urothelial carci­noma 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 is admin­istered at a fixed dose of 200 mg 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) cancer 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 (pem­bro­lizu­mab) in pediatric patients with MSI-H central nervous system cancers have not been estab­lish­ed.

In adult patients with MSI-H cancer, KEYTRUDA is admin­istered at a fixed dose of 200 mg 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 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.

Selected Important Safety Information for KEYTRUDA® (pem­bro­lizu­mab)

KEYTRUDA can cause immune-mediated pneu­mo­nitis, in­­clud­ing fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients re­ceiv­ing KEYTRUDA, in­­clud­ing Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneu­mo­nitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). 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.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients re­ceiv­ing KEYTRUDA, in­­clud­ing Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. 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.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients re­ceiv­ing KEYTRUDA, in­­clud­ing Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. 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.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients re­ceiv­ing KEYTRUDA, in­­clud­ing Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symp­toms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer cortico­steroids and hormone replacement as clin­i­cally indicated. Withhold KEYTRUDA for Grade 2; withhold or dis­con­tinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, in­­clud­ing hyperthyroidism, hypo­thy­roid­ism, and thyroiditis. Hyper­thyroidism occurred in 96 (3.4%) of 2799 patients re­ceiv­ing KEYTRUDA, in­­clud­ing Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, in­­clud­ing Grade 2 (6.2%) and 3 (0.1%) hypo­thy­roid­ism. Thyroiditis occurred in 16 (0.6%) of 2799 patients re­­ceiv­­ing KEYTRUDA, in­­clud­ing Grade 2 (0.3%) thyroiditis. 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 (pem­bro­lizu­mab) for Grade 3 or 4 hyper­­thyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, in­­clud­ing diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyper­glycemia or other signs and symp­toms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and admin­ister anti­hyper­gly­cemics in patients with severe hyper­gly­cemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients re­ceiv­ing KEYTRUDA, in­­clud­ing Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. 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.

KEYTRUDA can cause other clin­i­cally important immune-mediated adverse reac­tions. These immune-mediated reac­tions may occur in any organ system. 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 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 KEYTRUDA when the adverse reac­tion remains at Grade 1 or less fol­low­ing cortico­steroid taper. Permanently dis­con­tinue KEYTRUDA 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% (unless other­wise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syn­drome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addi­tion, myelitis and myocarditis were reported in other clin­i­cal trials, in­­clud­ing classical Hodgkin lym­phoma, and post­marketing use.

Solid organ trans­plant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may in­­crease the risk of rejection in solid organ trans­plant recipients. Consider the benefit of treat­ment with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA (pem­bro­lizu­mab) can cause severe or life-threatening infusion-related reac­tions, in­­clud­ing hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 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 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.

KEYTRUDA mono­therapy was dis­con­tinued due to adverse reac­tions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in perma­nent dis­con­tinu­a­tion of KEYTRUDA was pneu­mo­nitis (1.8%). Adverse reac­tions leading to inter­rup­tion of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneu­monia (1%), liver enzyme elevation (1.2%), de­creased appetite (1.3%), and pneu­mo­nitis (1%). The most common adverse reac­tions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were de­creased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

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.

Our Focus on Cancer

Our goal is to translate breakthrough science into inno­va­tive on­col­ogy medicines to help people with cancer world­wide. At Merck, 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, Merck 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 500 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.

For more in­­for­ma­tion about our on­col­ogy clin­i­cal trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global bio­pharma­ceu­tical com­pany known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most chal­leng­ing diseases. 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. Today, Merck con­tinues to be at the forefront of research to ad­vance the prevention and treat­ment of diseases that threaten people and communities around the world - in­­clud­ing cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases in­­clud­ing HIV and Ebola. For more in­­for­ma­tion, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) in­cludes “forward-looking state­ments” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These state­ments are based upon the current beliefs and ex­pec­ta­tions of the com­pany’s man­age­ment and are subject to sig­nif­i­cant risks and un­cer­tain­ties. There can be no guar­an­tees with respect to pipe­line prod­ucts that the prod­ucts will receive the nec­es­sary regu­la­tory approvals or that they will prove to be commercially successful. If under­lying assump­tions prove inaccurate or risks or un­cer­tain­ties materialize, actual results may differ materially from those set forth in the forward-looking state­ments.

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The com­pany under­takes no obli­ga­tion to publicly update any forward-looking state­ment, whether as a result of new in­­for­ma­tion, future events or other­wise. Additional factors that could cause results to differ materially from those described in the forward-looking state­ments can be found in the com­pany’s 2016 Annual Report on Form 10-K and the com­pany’s other filings with the Securities and Exchange Com­mis­sion (SEC) avail­able at the SEC’s Internet site (www.sec.gov).

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

Patient Information/Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

Source: Merck.