PHILADELPHIA, PA, USA I April 19, 2015 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of data investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in 25 patients with advanced pleural mesothelioma, a difficult-to-treat cancer of the lining of the lungs, abdomen and other organs. The early findings presented showed an overall response rate (confirmed and unconfirmed) of 28 percent with KEYTRUDA in patients with tumors that expressed PD-L1. Additionally, 48 percent of patients had stable disease, resulting in a disease control rate of 76 percent. These data, from KEYNOTE-028, will be presented today at the American Association for Cancer Research (AACR) Annual Meeting by Dr. Evan Alley, Abramson Cancer Center, University of Pennsylvania, and were part of the AACR official press program (abstract #CT103). This is the first data to be presented from KEYNOTE-028, Merck’s innovative basket trial designed to evaluate the efficacy and safety of KEYTRUDA in patients with 20 difficult-to-treat cancers.
“This presentation at AACR marks the first time that data involving an anti-PD-1 therapy have been presented in pleural mesothelioma, which is a rare, hard-to-treat cancer with very limited treatment options,” said Dr. Alley, clinical associate professor of medicine, Abramson Cancer Center. “While early, the disease control rates observed in this study are very encouraging, and indicate that further study is warranted to evaluate the potential role of KEYTRUDA in the treatment of malignant pleural mesothelioma.”
“This unique study is helping to accelerate our understanding of where KEYTRUDA may work in cancers with limited or no treatment options,” said Dr. Roger Dansey, therapeutic area head and senior vice president, oncology late stage development, Merck Research Laboratories. “These early data in advanced pleural mesothelioma reinforce the clinically meaningful results we are seeing with KEYTRUDA across multiple cancers.”
At the time of the analysis, 40 percent of patients (n=10/25) remained on treatment. Adverse events in the study were consistent with previously reported safety data for KEYTRUDA. The most common treatment-related adverse events (occurring in greater than twenty percent of patients) were fatigue (24%) and nausea (24%). Two Grade 3 treatment-related adverse events occurred: ALT increased (n=1) and thrombocytopenia (n=1). Some patients experienced adverse events of special interest, including rash (n=4), ALT/AST increased (n=1), hypersensitivity (n=1) and iridocyclitis (n=1); two required a dose interruption (one because of ALT/AST increased, one because of iridocyclitis). No patients discontinued as a result of treatment-related adverse events, and there were no treatment-related deaths.
About the KEYNOTE-028 Study
KEYNOTE-028 is an ongoing, multi-cohort, non-randomized Phase 1b basket trial evaluating the safety, tolerability, and anti-tumor activity of KEYTRUDA monotherapy (10 mg/kg dosed every two weeks) in 320 patients with PD-L1 positive advanced solid tumors that have not responded to current therapy or for which current therapy is not appropriate.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
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 unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. 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.
Merck is advancing a broad and fast-growing clinical development program for KEYTRUDA with more than 85 clinical trials – across more than 30 tumor types and over 14,000 patients – both as a monotherapy and in combination with other therapies.
Selected Important Safety Information for KEYTRUDA®
Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced melanoma receiving KEYTRUDA (the approved indication in the United States), including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively. 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 pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients respectively, 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 (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients, 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, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3; and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.
Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, 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.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, 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, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. 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 corticosteroids for Grade 3 or greater hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.
Other clinically important immune-mediated adverse reactions can occur. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of patients treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic neuritis, and rhabdomyolysis.
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. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or less. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
Based on its mechanism of action, KEYTRUDA may 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.
For the treatment of advanced melanoma, KEYTRUDA was discontinued for adverse reactions in 6% of 89 patients who received the recommended dose of 2 mg/kg and 9% of 411 patients across all doses studied. Serious adverse reactions occurred in 36% of patients receiving KEYTRUDA. The most frequent serious adverse drug reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in ≥20% of patients) were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).
The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. 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. Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.
About Malignant Mesothelioma
Malignant mesotheliomas are cancers of a covering tissue that lines the lung, abdomen, heart and testes. There are four main types of that are named based on where they develop: the chest (pleural mesotheliomas); the abdomen (peritoneal mesotheliomas); the covering around the heart (pericardial mesotheliomas); and the covering layer of the testicles (mesotheliomas of the tunica vaginalis). About 3,000 new cases of mesothelioma are diagnosed each year in the United States; about 75 percent of all cases are pleural mesotheliomas. The main risk factor for developing mesothelioma is exposure to asbestos; others include infection with simian virus 40 (SV40), older age (65 or older), and male gender.
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About Merck
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SOURCE: Merck
