KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced updated findings from a study evaluating KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in patients along with advanced cancers characterized as deficient for DNA mismatch repair (MMR). Results showed that among previously treated patients along with MMR-deficient tumors, there was an overall response price (ORR) of 53 percent (n=16/30) (95% CI, 36-70) in patients along with a range of advanced non-colorectal sturdy tumors and an ORR of 57 percent (n=16/28) (95% CI, 39-73) in patients along with advanced colorectal cancer; in contrast, no responses were observed in patients along with advanced colorectal cancer whose tumors were characterized as MMR-proficient (n=0/25). The findings, from a phase 2 study led by researchers from Johns Hopkins Kimmel Cancer Focus in collaboration along with Merck, were presented at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstracts #3003, #103).
“We keep on to be encouraged by the findings of this ongoing study evaluating KEYTRUDA in patients along with mismatch repair deficient tumors,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “Characterization of biomarkers along with the potential to predict clinical outcomes for patients receiving immune therapy for cancer is an vital element of our clinical program for KEYTRUDA.”
Merck is conducting a phase 2 registration study (KEYNOTE-164) to evaluate the efficacy and safety of KEYTRUDA monotherapy in patients along with previously treated, locally advanced unresectable or metastatic (Stage IV) MMR-deficient or microsatellite instability-higher (MSI-H) colorectal cancer and a phase 3 study (KEYNOTE-177) in a treatment-naïve patient population. One more phase 2 clinical trial (KEYNOTE-158) is evaluating patients along with advanced tumors classified as MSI-H, excluding colorectal carcinoma.
The KEYTRUDA (pembrolizumab) clinical development program entails much more compared to 30 tumor types in much more compared to 270 clinical trials, including much more compared to 100 trials that combine KEYTRUDA along with various other cancer treatments.
Updated Findings from Non-Colorectal Cancer Cohort (Abstract #3003) and Colorectal Cancer Cohort (Abstract #103)
The phase 2 study evaluated the clinical activity of KEYTRUDA monotherapy (10 mg/kg every two weeks) in patients along with previously treated, progressive metastatic disease along with or devoid of MMR-deficiency. Three groups were evaluated: MMR-deficient non-colorectal cancers (n=30), MMR-deficient colorectal cancer (n=28), and MMR-proficient colorectal cancer (n=25). MMR status was assessed locally using a standard immunohistochemistry (IHC) or polymerase chain reaction (PCR)-based way for detection of microsatellite instability. The Essential endpoints of the study were ORR, duration of response (DOR), progression-free survival (PFS) measured by RECIST v1.1, and overall survival (OS).
Abstract #3003 described findings from a cohort of patients along with MMR-deficient non-colorectal cancers (including ampullary/biliary, endometrial, gastric, pancreatic, prostate, sarcoma, and small bowel) that received KEYTRUDA. Results demonstrated an ORR of 53 percent (n=16/30) (95% CI, 36-70) – 30 percent were finish responses (n=9/30) and 23 percent were partial responses (n=7/30). Additionally, 17 percent of patients had steady disease (n=5/30), and the disease manage price was 70 percent (n=21/30) (95% CI, 52-83). Median PFS and OS were not reached at the time of analysis; median duration of follow-up was 10 months.
Abstract #103 described findings from two cohorts of patients along with colorectal cancer (MMR-deficient and MMR-proficient) that received KEYTRUDA. Among those patients along with MMR-deficient tumors, an ORR of 57 percent was observed (n=16/28) (95% CI, 39-73) – 11 percent were finish responses (n=3/28) and 46 percent were partial responses (n=13/28). Additionally, 32 percent of patients had steady disease (n=9/28) and the disease manage price was 89 percent (n=25/28) (95% CI, 73-96). The median PFS and OS were not reached; median duration of follow-up was 9.3 months. Among patients along with MMR-proficient tumors, no responses were observed (n=0/25) and the disease manage price was 16 percent (n=4/25) (95% CI, 6-35); 16 percent had steady disease (n=4/25). Additionally, in patients along with MMR-proficient tumors, the median PFS was 2.3 months and the median OS was 5.98 months; median duration of follow-up was 6 months.
The safety profile of KEYTRUDA (pembrolizumab) was consistent along with that observed in previously reported studies. For patients in the MMR-deficient non-colorectal cancers cohort, Grade 3-4 treatment-related edge events included diarrhea/colitis (n=3) and pancreatitis (n=1). For patients in the colorectal cancer cohorts (MMR-deficient and MMR-proficient), Grade 3-4 treatment-related edge events included diarrhea/colitis (n=1), pancreatitis (n=2), rash/pruritus (n=1), anemia (n=1), leukopenia (n=1), and thrombocytopenia (n=1).
Initial findings from this study evaluating KEYTRUDA (41 patients) were presented at the 2015 ASCO Annual Meeting and simultaneously published online in the New England Diary of Medicine (Le et al. Brand-new Eng. J. Med. 372, 26, 2509). On November 2, 2015, Merck announced that the U.S. Meals and Drug Administration (FDA) granted Breakthrough Therapy Designation to KEYTRUDA for the treatment of patients along with MSI-H metastatic colorectal cancer.
About DNA Mismatch Repair and Microsatellite Instability
Analysis of tumor DNA for microsatellite instability Can easily be used to identify tumors along with defective DNA mismatch repair (MMR) systems. DNA MMR is a process that in normal cells permits the recognition and repair of genetic mismatches generated throughout DNA replication. A defective MMR system results in the persistence of DNA mismatches that could after that be incorporated in to the genetic code as mutations. The standard tumor has actually dozens of mutations; however, tumors along with DNA MMR-deficiency could harbor thousands, especially in regions of repetitive DNA known as microsatellites. Tumors that are found to have actually mutations in choose microsatellite sequences, called microsatellite instability (MSI), are considered DNA MMR-deficient. These tumors are referred to as being “MSI-high.” Overall, DNA MMR-deficiency is present in approximately 15-20 percent of tumors in Stage II disease, 10 percent in Stage III disease and approximately 5 percent or much less in Stage IV disease. In colorectal cancers, MMR-deficiency is seen in approximately 15-20 percent of non-hereditary colorectal cancers and in most hereditary colorectal cancers associated along with Lynch Syndrome.
About KEYTRUDA®(pembrolizumab) Injection 100 mg
KEYTRUDA is a humanized monoclonal antibody that works by increasing the skill of the body’s immune system to assistance 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 could affect both tumor cells and healthy and balanced cells.
KEYTRUDA (pembrolizumab) is indicated for the treatment of patients along with unresectable or metastatic melanoma.
KEYTRUDA is additionally indicated for the treatment of patients along with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test along with disease progression on or after platinum-containing chemotherapy. Patients along with EGFR or ALK genomic tumor aberrations need to have actually disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. This indication is approved under accelerated approval based on tumor response price and durability of response. An improvement in survival or disease-related symptoms has actually not yet been established. Continued approval for this indication could 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 vital Safety Short article for KEYTRUDA® (pembrolizumab)
Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients along with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients along with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and much more regularly in patients along 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 along with radiographic imaging. Administer corticosteroids for Grade 2 or better pneumonitis. Withhold KEYTRUDA for Grade 2; forever discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Immune-mediated colitis occurred in 31 (2%) of 1567 patients along 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 along 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 better colitis. Withhold KEYTRUDA for Grade 2 or 3; forever discontinue KEYTRUDA for Grade 4 colitis.
Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Hepatitis occurred in 16 (1%) of 1567 patients along with melanoma, including Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. Monitor patients for adjustments in liver function. Administer corticosteroids for Grade 2 or better hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 13 (0.8%) of 1567 patients along with melanoma, including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. Hypophysitis occurred in 1 (0.2 %) of 550 patients along 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 substitute 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 along with melanoma, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1567 patients along with melanoma, including Grade 3 (0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550 patients along with NSCLC, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients along with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders Can easily occur at any kind of time throughout treatment. Monitor patients for adjustments in thyroid function (at the start of treatment, periodically throughout treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer substitute hormones for hypothyroidism and control hyperthyroidism along with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA (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 various other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti hyperglycemics in patients along with severe hyperglycemia.
Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 7 (0.4%) of 1567 patients along with melanoma including, Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. Monitor patients for adjustments in renal function. Administer corticosteroids for Grade 2 or better nephritis. Withhold KEYTRUDA for Grade 2; forever discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically vital immune-mediated edge reactions Can easily occur. For suspected immune-mediated edge reactions, guarantee adequate evaluation to confirm etiology or exclude various other causes. Based on the severity of the edge reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and keep on to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related edge reactions could not be controlled along with corticosteroid use, administration of various other systemic immunosuppressants Can easily be considered. Return to KEYTRUDA as quickly as the edge reaction remains at Grade 1 or much less adhering to corticosteroid taper. forever discontinue KEYTRUDA (pembrolizumab) for any kind of Grade 3 immune-mediated edge reaction that recurs and for any kind of life-threatening immune-mediated edge reaction.
The adhering to clinically significant, immune-mediated edge reactions occurred in much less compared to 1% (unless otherwise indicated) of 1567 patients along 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 along with inflammatory foci in brain parenchyma. The adhering to clinically significant, immune-mediated edge reactions occurred in much less compared to 1% of 550 patients along with NSCLC: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions have actually 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 forever discontinue KEYTRUDA (pembrolizumab).
Based on its mechanism of action, KEYTRUDA Can easily create fetal harm as quickly as administered to a pregnant woman. If used throughout pregnancy, or if the patient becomes pregnant throughout treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception throughout treatment and for 4 months after the last dose of KEYTRUDA.
In Trial 6, KEYTRUDA was discontinued as a result of edge reactions in 9% of 555 patients along with advanced melanoma; edge reactions leading to discontinuation in much more compared to one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). edge reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common edge reactions along with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% along with KEYTRUDA), rash (24% vs 23%), and nausea (21% along with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those edge reactions that occurred at the same or lower price compared to along with KEYTRUDA.
In Trial 2, KEYTRUDA was discontinued as a result of edge reactions in 12% of 357 patients along with advanced melanoma; the most common (≥1%) were general bodily good health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). edge 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 edge reactions along with KEYTRUDA vs chemotherapy were fatigue (43% along with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% along with KEYTRUDA), diarrhea (20% vs 20%), and decreased cravings (20% along with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those edge reactions that occurred at the same or lower price compared to along with KEYTRUDA (pembrolizumab).
KEYTRUDA was discontinued as a result of edge reactions in 14% of 550 patients along with NSCLC. Serious edge reactions occurred in 38% of patients. The most frequent serious edge reactions reported at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common edge reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased cravings (25%), and dyspnea (23%).
No formal pharmacokinetic drug interaction studies have actually been conducted along with KEYTRUDA.
It is not known whether KEYTRUDA is excreted in human milk. Since numerous drugs are excreted in human milk, instruct women to discontinue nursing throughout treatment along with KEYTRUDA and for 4 months after the last dose.
Safety and effectiveness of KEYTRUDA have actually not been established in pediatric patients.
Our Concentrate on Cancer
Our target is to translate breakthrough science in to innovative oncology medicines to assistance individuals along with cancer worldwide. At Merck Oncology, aiding individuals 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 quest – from lab to clinic – to potentially bring Brand-new chance to individuals along with cancer.
As portion of our Concentrate on cancer, Merck is committed to exploring the potential of immuno-oncology, along with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that entails much more compared to 270 clinical trials evaluating our anti-PD-1 therapy across much more compared to 30 tumor types. We additionally keep on to strengthen our immuno-oncology portfolio through strategic acquisitions and prioritizing the development of several promising immunotherapeutic candidates along with the potential to improve the treatment of advanced cancers.
For much more Short article Regarding our oncology clinical trials, visit http://ift.tt/1np5kw2.
About Merck
For 125 years, Merck has actually been a global good health care leader working to assistance the globe be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal good health products, we job along with customers and operate in much more compared to 140 countries to deliver innovative good health solutions. We additionally demonstrate our commitment to increasing access to good health care through far-reaching policies, programs and partnerships. For much more information, visit www.merck.com and connect along with us on Twitter, Facebook, YouTube and LinkedIn.
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Please see Prescribing Short article for KEYTRUDA (pembrolizumab) at http://ift.tt/1np5nrw and Patient Information/Medication Guide for KEYTRUDA at http://ift.tt/1np5nrB.
