KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced new data with KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy from two studies (KEYNOTE-012 and KEYNOTE-055) in heavily pre-treated patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Data are being presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

In KEYNOTE-012, for the primary endpoint, findings showed an overall response rate (ORR) of 18 percent (n=34/192) (95% CI, 13-24). At the time of analysis, 65 percent of responders (n=22/34) were continuing to respond – with responses observed in some patients for more than 30 months; median duration of response had not yet been reached. The secondary endpoint results showed a median overall survival (OS) rate of eight months (95% CI, 6-10) (Abstract #6012). The phase 1b KEYNOTE-012 study was the first clinical study investigating the role of a PD-1 inhibitor in recurrent or metastatic HNSCC. Based on the results of KEYNOTE-012, Merck is seeking approval for KEYTRUDA (200 mg fixed dose every three weeks) for previously treated recurrent or metastatic HNSCC. The U.S. Food and Drug Administration (FDA) granted Priority Review with a PDUFA, or action date, of August 9, 2016. The application will be reviewed under the FDA’s Accelerated Approval program.

For the second study, KEYNOTE-055, which enrolled patients regardless of PD-L1 tumor status, an analysis based on the first 50 patients showed an ORR (confirmed, partial responses) in nearly one in five, or 18 percent (n=9/50) (95% CI, 9-31) of patients treated with KEYTRUDA (Abstract #6011). Findings from 92 patients with six months of follow-up or more are also being presented. KEYNOTE-055 is a phase 2 study evaluating the safety, tolerability, and anti-tumor activity of KEYTRUDA (pembrolizumab) as a monotherapy (200 mg fixed dose every three weeks) in patients with recurrent or metastatic HNSCC with disease progression on platinum-based and cetuximab therapy.

“Head and neck cancer is an extremely difficult disease to treat – and despite our best efforts, bringing forward meaningful treatment advances has been challenging,” said Dr. Ranee Mehra, chief of head and neck oncology, Fox Chase Cancer Center. “To see this level of response with pembrolizumab in patients with head and neck cancer is encouraging and provides further evidence of the potential for pembrolizumab in the treatment of this disease.”

The KEYTRUDA clinical development program includes more than 30 tumor types in more than 270 clinical trials, including more than 100 trials that combine KEYTRUDA with other cancer treatments. With four registration-enabling studies, Merck currently has the largest immuno-oncology clinical development program in head and neck cancer, encompassing all stages of advanced disease, and is conducting research investigating OS and progression-free survival (PFS) endpoints with KEYTRUDA as a monotherapy, as well as in combination with chemotherapy compared to standard of care.

“In Merck’s immuno-oncology clinical development program, we are rapidly evaluating the potential for KEYTRUDA to play a role in managing a range of difficult-to-treat cancers, and these data being presented at ASCO are the result of this effort,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We look forward to bringing KEYTRUDA to more patients with our application for advanced head and neck cancer.”

Findings from the KEYNOTE-012 Study (Abstract #6012)

KEYNOTE-012 is an ongoing multicenter, non-randomized, open-label, multi-cohort phase 1b trial evaluating KEYTRUDA as a monotherapy (10 mg/kg every two weeks or 200 mg fixed dose every three weeks) in patients with various advanced cancers, including head and neck. The head and neck cohorts include patients with recurrent or metastatic HNSCC, regardless of tumor human papilloma virus (HPV) status (23% positive; 77% negative). One cohort includes 60 patients who were considered PD-L1 positive; a second cohort includes 132 patients, regardless of PD-L1 tumor status. The primary endpoints include overall safety, tolerability, and ORR (as measured by RECIST v1.1); secondary endpoints include PFS, OS, and duration of response.

Findings presented at ASCO were based on long-term follow-up of a pooled analysis of the total population of patients across the two head and neck cohorts (n=192). Data showed an ORR (confirmed) of 18 percent (n=34/192) (95% CI, 13-24) – including eight complete responses and 26 partial responses. Thirty-three patients had stable disease and 93 patients had progressive disease. In total, 60 percent of patients experienced a decrease in their target lesions at the time of analysis. The median time to response was two months (range, 2-17 months). While median duration of response had not yet been reached (range, 2+ to 30+ months), 65 percent of responders (n=22/34) were continuing to respond at the time of analysis (85 percent of responses lasted for six months or more with 71 percent lasting for 12 months or more). An analysis of the survival measurements showed a median PFS of two months (95% CI, 1.9-2.1) – with a six-month PFS rate of 25 percent and 12-month PFS rate of 17 percent. The median OS was eight months (95% CI, 6-10) – with a six-month OS rate of 58 percent and a 12-month OS rate of 38 percent.

The safety profile was consistent with that observed in previously reported KEYTRUDA (pembrolizumab) studies. The treatment-related adverse events observed in this trial (any grade occurring in 5 percent or more of patients) were fatigue (n=42), hypothyroidism (n=19), rash (n=18), pruritus (n=16), decreased appetite (n=16), pyrexia (n=12), and nausea (n=11). Grade 3-4 treatment-related adverse events observed (occurring in 2 or more patients) were ALT increase (n=3), AST increase (n=3), fatigue (n=2), decreased appetite (n=2), hyponatremia (n=2), pneumonitis (n=2), facial swelling (n=2), and hypothyroidism (n=2). Twelve patients discontinued due to a treatment-related adverse event; there were no treatment-related deaths.

These data are being presented today, June 6, in an oral session by Dr. Ranee Mehra of Fox Chase Cancer Center from 12:18 – 12:30 p.m. CDT (Location: S100bc).

Findings from the KEYNOTE-055 Study (Abstract #6011)

KEYNOTE-055 is an ongoing multicenter phase 2 trial evaluating KEYTRUDA as a monotherapy (200 mg fixed dose every three weeks) in patients with advanced HNSCC, regardless of PD-L1 status, who have progressed on platinum-based and cetuximab therapy. The primary endpoints include overall safety, tolerability, and ORR (as measured by RECIST v1.1); secondary endpoints include PFS, OS, and duration of response.

Data presented at ASCO were based on an early analysis conducted on the first 50 patients enrolled in the study to receive KEYTRUDA and on an analysis of 92 patients with six months of follow-up or more. The first analysis (n=50) showed an ORR (confirmed, partial responses) of 18 percent (n=9/50) (95% CI, 9-31); nine patients had stable disease and 30 had progressive disease.

The analysis of the results observed in patients with six or more months follow-up (n=92) showed an ORR (confirmed, partial responses) of 17 percent (n=16/92) (95% CI, 10-27); 17 patients had stable disease and 51 had progressive disease. Analysis of results based on tumor HPV status showed an ORR of 22 percent (n=4/18) (95% CI, 6-48) in HPV-positive patients and 16 percent (n=12/74) (95% CI, 9-27) in HPV-negative patients. An analysis based on PD-L1 expression showed an ORR of 17 percent (n=13/76) (95% CI, 9-28) in patients whose tumors expressed PD-L1 and eight percent (n=1/13) (95% CI, 0.2-36) in patients whose tumors did not express PD-L1. Overall, 54 percent experienced a decrease in their target lesions. The median time to response was two months (range, 2-5 months). Median follow-up duration was seven months (range, 0-14 months) with 75 percent of responders remaining in response at the time of analysis. An analysis of the survival measurements showed a median PFS of 2.1 months (95% CI, 2.0-2.3), with a six-month PFS rate of 24 percent, and a median OS of eight months (95% CI, 8-11), with a six-month OS rate of 65 percent.

The safety profile was consistent with that observed in previously reported

KEYTRUDA (pembrolizumab) studies. The treatment-related adverse events observed in this trial (any grade occurring in five percent or more of patients) were fatigue (n=20), hypothyroidism (n=13), diarrhea (n=10), decreased appetite (n=9), nausea (n=9), AST increase (n=9), and rash (n=9). Grade 3-5 treatment-related adverse events observed (occurring in 2 or more patients) were anemia (n=2), AST increase (n=2), Alkaline Phosphatase increase (n=2), and hepatitis (n=2). There was one treatment-related death due to pneumonitis; three additional patients discontinued due to a treatment-related adverse event.

These data are being presented today, June 6, in an oral session by Dr. Joshua Bauml of the University of Pennsylvania from 12:06 – 12:18 p.m. CDT (Location: S100bc).

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 for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA (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 KEYTRUDA. 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.

KEYTRUDA 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 KEYTRUDA ^®  (pembrolizumab)

Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. 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 and 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 KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 31 (2%) of 1567 patients with melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC, 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 KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including Grade 2 (0.1%), 3 (0.7%), 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.

Hypophysitis occurred in 13 (0.8%) of 1567 patients with melanoma, including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. 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 clinically indicated. Withhold KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3 (0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, 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 KEYTRUDA 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 insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including, Grade 2 (0.2%), 3 (0.2%), 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.

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 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 1567 patients with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, 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: 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 KEYTRUDA (pembrolizumab).

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.

In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA (pembrolizumab).

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients with NSCLC. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported 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 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.

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 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 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 125 years, Merck has been 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

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