KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced findings from three divide studies evaluating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in combination along with others treatment regimens including talimogene laherparepvec, dabrafenib plus trametinib, or low-dose ipilimumab in patients along with advanced melanoma. These data, from MASTERKEY-265, KEYNOTE-022, and KEYNOTE-029, respectively, are included in the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstracts #9568, #3014, and #9506).
“We keep on to build on our leadership in advanced melanoma by evaluating KEYTRUDA along with multiple combination partners utilizing diverse mechanisms of action along with the objective of boosting outcomes while maintaining tolerability,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “These encouraging early data point to the potential for KEYTRUDA to become an crucial component of combination therapy in melanoma.”
Each of these studies was created to answer personal questions about the use of KEYTRUDA in various combination treatment settings. In each of the three studies, the safety profile of the combination regimens was shown to be manageable.
“Anti-PD-1 drug therapies, adore pembrolizumab, have actually shown benefit as a monotherapy in the treatment of advanced melanoma, and it is crucial to understand their potential in combination along with others effective therapeutics, including immunotherapies and targeted therapies,” said Dr. Georgina Long, professor of melanoma medical oncology and translational melanoma research, Melanoma Institute Australia and University of Sydney. “Physicians are focused on different treatment paths for different types of patients and, along with the promising data presented at ASCO this year, we aim to much better understand the role of monotherapy and make combination treatment strategies for patients along with advanced melanoma that could not benefit as much from monotherapy.”
The KEYTRUDA (pembrolizumab) clinical development program entails patients along with a lot more compared to 30 tumor types in a lot more compared to 270 ongoing or planned studies, including a lot more compared to 100 trials that combine KEYTRUDA along with others cancer treatments – these include others immuno-oncology therapies, standard therapies and targeted therapies.
Findings from MASTERYKEY-265: KEYTRUDA along with talimogene laherparepvec (Abstract #9568)
MASTERKEY-265 is an ongoing phase 1b study evaluating the safety, efficacy, and tolerability of KEYTRUDA in combination along with talimogene laherparepvec in patients along with previously untreated, unresectable advanced melanoma. The trial is a collaboration between Merck and Amgen. Talimogene laherparepvec is a herpes simplex virus-1 (HSV-1)-based oncolytic immunotherapy used for the treatment of melanoma lesions in the skin and lymph nodes.
Updated data from 21 evaluable patients showed that a combination of KEYTRUDA (200 mg every two weeks) along with talimogene laherparepvec (up to 4 mL of 106 PFU/mL, after that 108 PFU/mL every two weeks) resulted in a confirmed overall response fee (ORR) of 57.1 percent (n=12/21) (95% CI, 34-78.2), per modified immune-related response criteria (irRC) – 23.8 percent were finish responses (n=5/21) and 33.3 percent were partial responses (n=7/21).
The safety profile of KEYTRUDA in combination along with talimogene laherparepvec was consistent along with that observed in previously reported studies of KEYTRUDA or talimogene laherparepvec monotherapy in patients along with advanced melanoma. Seven patients (33%) endured treatment-related Grade 3-4 edge events, including: anemia, aseptic meningitis, autoimmune hepatitis, generalized rash, headache, hyperglycemia, hypoglycemia, hypophosphatemia, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma-glutamyltransferase, muscle spasms, macular rash, rash, and pneumonitis. Two patients (10%) endured a treatment-related edge event that led to permanent discontinuation of KEYTRUDA. No patients (0%) endured a treatment-related edge event that led to permanent discontinuation of talimogene laherparepvec. No dose-limiting toxicities were reported.
These data were presented by Dr. Long on June 4.
Findings from KEYNOTE-022: KEYTRUDA along with dabrafenib plus trametinib (Abstract #3014)
KEYNOTE-022 is an ongoing phase 1/2 study created to assess the safety and efficacy of KEYTRUDA in combination along with dabrafenib plus trametinib in patients along with advanced melanoma. Dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) is a combination regimen used in the treatment of certain types of advanced melanoma.
Based on early data from the 15 patients treated in phase 1, treatment along with KEYTRUDA (pembrolizumab) (2 mg/kg every three weeks) along with dabrafenib (150 mg two times daily) plus trametinib (2 mg daily) resulted in nine partial responses, 5 of which were confirmed. Additionally, of the patients along with lesion data available, 92.3 percent endured a reduction in tumor size (n=12/13).
Grade 3-4 edge events occurring in higher compared to or equal to 10 percent of patients included ALT increased (n=3), AST increased (n=3), pyrexia (n=3), GGT increased (n=2), and WBC count decreased (n=2). Four patients (26.7%) endured a treatment-related edge even that led to discontinuation. There were no treatment-related deaths. The phase 2 portion of the study is ongoing and will certainly further evaluate the safety and efficacy of the KEYTRUDA combination regimen compared to dabrafenib plus trametinib.
On June 5, these data will certainly be presented by Dr. Antoni Ribas in a poster session from 8:00 – 11:30 a.m. CDT (Location: Hall A) and in a poster discussion from 4:45 – 6:00 p.m. CDT (Location: Hall B1).
Findings from KEYNOTE-029: KEYTRUDA along with low-dose ipilimumab (Abstract #9506)
KEYNOTE-029 is an ongoing phase 1/2 study evaluating the safety, efficacy, and tolerability of KEYTRUDA in combination along with low-dose ipilimumab in patients along with advanced melanoma. Ipilimumab is a CTLA-4 inhibitor used in the treatment of melanoma.
Findings from 153 evaluable patients along with advanced melanoma showed that KEYTRUDA (2 mg/kg every three weeks) in combination along with low-dose ipilimumab (1 mg/kg every three weeks for four doses) demonstrated an ORR of 57 percent (95% CI, 49-65) by independent central review – 10 percent were finish responses (n=15/153) and 47 percent were partial responses (n=72/153). The six-month progression-free survival (PFS) fee was 70 percent and the six-month overall survival (OS) fee was 93 percent. At the time of analysis, median PFS (95% CI, 12.4 months-NR) and OS (95% CI, NR-NR) were not reached; 98 percent of responses were ongoing. Median follow-up duration was 10.0 months (range 0.8-14.1).
Sixty-four patients (42%) endured treatment-related Grade 3-4 edge events. Thirty-eight patients (25%) endured immune-mediated Grade 3-4 edge events, including: colitis, hepatitis, hyperthyroidism, hypophysitis, infusion reaction, pancreatitis, pneumonitis, nephritis, skin reactions, and type 1 diabetes mellitus. Sixteen patients (10%) endured a treatment-related edge event that led to ipilimumab discontinuation only, 11 patients (7%) endured a treatment-related edge event that led to KEYTRUDA (pembrolizumab) discontinuation after completion or discontinuation of ipilimumab, and 16 patients (10%) endured a treatment-related edge event that led to ipilimumab and KEYTRUDA discontinuation, including one patient that discontinued ipilimumab for colitis and later discontinued KEYTRUDA for increased lipase. There were no treatment-related deaths.
These data will certainly be presented in an oral session by Dr. Long on June 6 at 2:51 p.m. CDT (Location: Arie Crown Theater).
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 suggestions 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 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 must 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 fee 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 crucial Safety Write-up for KEYTRUDA® (pembrolizumab)
Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis along with radiographic imaging. Administer corticosteroids for Grade 2 or higher pneumonitis. Withhold KEYTRUDA for Grade 2; completely discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Immune-mediated colitis occurred in 31 (2%) of 1567 patients, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or higher colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3; completely discontinue KEYTRUDA for Grade 4 colitis.
Immune-mediated hepatitis occurred in 16 (1%) of 1567 patients, 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 higher hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 13 (0.8%) of 1567 patients, including Grade 2 (0.3%), 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 alternative as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1567 patients, including Grade 3 (0.1%) hypothyroidism. Thyroid disorders Can easily occur at any type 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 alternative hormones for hypothyroidism and control hyperthyroidism along 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 others 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 7 (0.4%) of 1567 patients, 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 higher nephritis. Withhold KEYTRUDA for Grade 2; completely discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically crucial immune-mediated edge reactions Can easily occur. For suspected immune-mediated edge reactions, make sure adequate evaluation to confirm etiology or exclude others 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 others systemic immunosuppressants Can easily be considered. Return to KEYTRUDA as soon as the edge reaction remains at Grade 1 or much less adhering to corticosteroid taper. completely discontinue KEYTRUDA for any type of Grade 3 immune-mediated edge reaction that recurs and for any type 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: 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.
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 completely discontinue KEYTRUDA (pembrolizumab).
Based on its mechanism of action, KEYTRUDA Can easily create fetal harm as soon 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; edge reactions leading to discontinuation in a lot 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 fee compared to along with KEYTRUDA.
In Trial 2, KEYTRUDA was discontinued as a result of edge reactions in 12% of 357 patients; the most common (≥1%) were general bodily healthiness 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 hunger (20% along with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those edge reactions that occurred at the same or lower fee compared to along with KEYTRUDA.
No formal pharmacokinetic drug interaction studies have actually been conducted along with KEYTRUDA.
It is not known whether KEYTRUDA is excreted in human milk. Due to the fact that 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 (pembrolizumab) have actually not been established in pediatric patients.
Our Concentrate on Cancer
Our objective is to translate breakthrough science in to innovative oncology medicines to suggestions 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 a lot more compared to 270 clinical trials evaluating our anti-PD-1 therapy across a lot more compared to 30 tumor types. We additionally keep on to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates along with the potential to improve the treatment of advanced cancers.
For a lot more Write-up Regarding our oncology clinical trials, visit http://ift.tt/1np5kw2.
About Merck
For 125 years, Merck has actually been a global healthiness care leader working to suggestions the globe be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal healthiness products, we job along with customers and operate in a lot more compared to 140 countries to deliver innovative healthiness solutions. We additionally demonstrate our commitment to increasing access to healthiness care through far-reaching policies, programs and partnerships. For a lot more information, visit www.merck.com and connect along with us on Twitter, Facebook, 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”) entails “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 latest beliefs and expectations of the company’s management and are subject to considerable risks and uncertainties. There Can easily be no guarantees along with respect to pipeline products that the products will certainly receive the important regulatory approvals or that they will certainly prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results could differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include yet are not limited to, general industry conditions and competition; general economic factors, including interest fee and currency exchange fee fluctuations; the impact of pharmaceutical industry regulation and healthiness care legislation in the United States and internationally; global trends toward healthiness care cost containment; technological advances, brand-new products and patents accomplished by competitors; challenges inherent in brand-new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of global economies and sovereign risk; dependence on the effectiveness of the company’s patents and others protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any type of forward-looking statement, whether as a result of brand-new information, future events or otherwise. Additional factors that could create results to differ materially from those described in the forward-looking statements Can easily be found in the company’s 2015 Annual Report on Form 10-K and the company’s others filings along with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Write-up for KEYTRUDA (pembrolizumab) at http://ift.tt/1np5nrw and
Patient Information/Medication Guide for KEYTRUDA at http://ift.tt/1np5nrB.
