On December 5, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported the oral presentation of positive clinical data from its ongoing SL-401 Phase 2 potentially pivotal clinical trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Stemline Therapeutics, DEC 5, 2016, View Source [SID1234516936]). The trial results were delivered via an oral presentation by Naveen Pemmaraju, M.D., from the University of Texas MD Anderson Cancer Center, on Sunday morning at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, being held at the San Diego Convention Center in San Diego, CA.

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The full presentation is now available on the Stemline website, under the "Scientific Presentations" tab (see link: View Source).

The Phase 2 BPDCN data presented at ASH (Free ASH Whitepaper) cover 32 evaluable adult BPDCN patients treated with SL-401. Results demonstrated that SL-401 produced a 100% (16/16) overall response rate (ORR), including an 81% (13/16) complete response (CR) rate in first-line BPDCN patients treated at the recommended dose of 12 ug/kg/day and a 95% (18/19) ORR in first-line patients treated at the recommended dose or lower. In relapsed/refractory patients, the ORR was 69% (9/13) with a CR rate of 31% (4/13). See Tables 1 and 2 for a summary of efficacy and safety.

Response duration data continue to appear promising, with 69% (11/16) first-line BPDCN patients treated at 12 ug/kg/day remaining relapse-free (range: 1+ to 20+ months, ongoing). This includes four patients receiving SL-401 therapy (range: 1+ to 15+ months, ongoing), six patients in durable remission from SL-401 who were then successfully bridged to stem cell transplant (SCT) and remain in remission (range: 5+ to 20+ months progression-free after first SL-401 dose), and one additional patient undergoing SCT preparation. In the relapsed/refractory setting, 46% (6/13) patients are relapse-free (range: 1+ to 7+ months). This includes five patients receiving SL-401 therapy (range: 1+ to 4+ months, ongoing) and one patient in durable remission from SL-401 who was then successfully bridged to SCT and remains in remission for approximately 8+ months, ongoing. The median progression-free and overall survival for first-line has not been reached and for relapsed/refractory it is currently 8.5 months.

Naveen Pemmaraju, M.D., Assistant Professor, Department of Leukemia at the University of Texas MD Anderson Cancer Center (Houston, TX), an investigator on the study, commented, "The encouraging results generated to date with SL-401 continue to indicate the agent could very well emerge as the standard of care for both first-line and relapsed/refractory BPDCN, a devastating disease for which there had previously been no effective therapy. In addition to strong clinical activity, manifested by high levels of durable responses, the safety profile with SL-401 continues to be predictable and manageable over increasing patient experience." Dr. Pemmaraju continued, "Together with Stemline, we are working to bring this promising new agent to patients as expeditiously as possible in BPDCN and other malignancies."

Andrew A. Lane, M.D., Ph.D., Assistant Professor, Medical Oncology at the Dana-Farber Cancer Institute (Boston, MA), and a co-investigator on the study, commented, "The clinical outcomes seen with SL-401 in first-line and relapsed/refractory BPDCN continue to be exciting, particularly given that these are two greatly under-served patient populations. SL-401 has also begun to show early promising signs in other clinical settings." Dr. Lane continued, "We are very pleased to be ongoing contributors to this study, and look forward to helping to advance this active agent in BPDCN and other hematologic malignancies as well."

Table 1. SL-401 Summary of Clinical Efficacy

Line of Therapy First-line First-line R/R All lines
Dose Group All Doses 12 ug/kg 12 ug/kg All Doses
n (evaluable/total) 19 16 13 32
ORR 18/19 (95%) 16/16 (100%) 9/13 (69%) 27/32 (84%)
CR*, n (rate) 14 (74%) 13 (81%) 4 (31%) 18 (56%)
Bridged to SCT, n 6 6 1 7 (22%)
(allo+auto) (3+3) (3+3) (1+0) (4+3)
*CR includes CRi (CR with incomplete hematopoietic recovery) and CRc (CR in non-skin organs and gross reduction in cutaneous lesions with residual microscopic disease).

Table 2. Most Common Adverse Events (≥ 15% treatment-related adverse effects, TRAEs)

All Grades (% of patients) Grade ≥ 3 (% of patients)
TRAEs All AEs TRAEs All AEs
Transaminase elevation 52 60 40 42
Hypoalbuminemia 39 42 0 0
Chills 31 35 0 0
Pyrexia 27 42 0 0
Nausea 23 46 0 0
Fatigue 23 42 0 8
Thrombocytopenia 19 19 19 19
Hypotension 19 19 0 0
Weight increased 19 27 0 0
Capillary leak syndrome (CLS) 19 19 8 8
Anemia 19 31 11 15
Decreased appetite 19 23 0 0
Edema peripheral 23 46 0 0

On December 5, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, and Northwestern University reported they signed a five-year collaboration agreement with the goal of advancing research and discovery in oncology (Press release, AbbVie, DEC 5, 2016, View Source [SID1234516933]). Together, AbbVie and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University will work in several areas of oncology research, which in addition to others could include, lung, colorectal, breast, prostate and hematological cancer.

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"One of the best steps AbbVie can take to deliver new therapies in oncology is to combine our research and discovery expertise with the talents and insight of our colleagues in academic medicine," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie. "The opportunity to work with leading researchers and clinicians from the Lurie Cancer Center enhances AbbVie’s ability to help oncology patients even more in the future."

The collaboration provides Lurie Cancer Center scientists with the opportunity to access new therapies developed by AbbVie for preclinical research funded under the agreement. Lurie Cancer Center scientists will also work closely with AbbVie’s research teams to support scientific knowledge exchange. In addition, the agreement provides AbbVie with the option to obtain an exclusive license of certain Lurie Cancer Center discoveries made as a result of the five-year collaboration.

"The ability to investigate new therapeutic agents with AbbVie provides us with a great opportunity to expand our translational oncology efforts," said Leonidas C. Platanias, M.D., Ph.D., director of the Lurie Cancer Center. "Our partnership with AbbVie will facilitate and accelerate the development of innovative new therapies against a wide variety of different cancers."

A joint steering committee comprised of representatives from both organizations will determine the research projects that the collaboration will undertake. Researchers from AbbVie and the Lurie Cancer Center will also hold a symposium at least once each year to discuss their joint research and potential ideas for new research projects.

On December 5, 2016 Pfizer Inc. and its partner Avillion LLP reported results from the Phase 3 BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment) trial demonstrating superiority of BOSULIF (bosutinib) over imatinib as a first-line treatment for patients with chronic phase Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) (Press release, Pfizer, DEC 5, 2016, View Source [SID1234516930]). The study met its primary endpoint of major molecular response (MMR) at 12 months. No new or unexpected safety issues were identified. BOSULIF is currently indicated in the U.S. and EU for the treatment of adult patients with Ph+ CML with resistance or intolerance to prior therapy.

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"Since its approval, the efficacy and distinct tolerability profile of BOSULIF has provided an important treatment option for patients with Ph+ CML who are resistant or intolerant to prior therapy. The positive outcome of the BFORE study represents a key step in potentially broadening treatment options for patients in the first-line setting," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "This is an important milestone for Pfizer’s emerging hematology portfolio as we work to develop new treatments for patients with acute and chronic hematologic malignancies."

"This successful partnership between Pfizer and Avillion is good news for CML patients because additional first-line treatment options allow physicians to tailor therapy based on individual patient considerations," said Allison Jeynes-Ellis, MD, Chief Executive Officer of Avillion. "The outcome of this partnership reinforces our belief in the potential of our innovative business model for the co-development and partnership of late-stage clinical candidates."

Based on the results of the study, Pfizer will work with the U.S. Food and Drug Administration (FDA) and other regulatory authorities to potentially make BOSULIF available for Ph+ CML patients in the first-line setting. Detailed efficacy and safety data from this study will be submitted for a future congress or peer-reviewed journal.

Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial. Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data that will be used to support potential regulatory filings for marketing authorization of BOSULIF as first-line treatment of patients with chronic phase Ph+ CML. If approved for this indication, Avillion will be eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize BOSULIF globally.

Pfizer is advancing a broad range of therapies that leverage select pathways and mechanisms of action to address acute and chronic leukemias, myeloproliferative disorders and lymphoma.

About the BFORE Study

BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment) is a multi-center, open-label Phase 3 study designed to assess the effectiveness and safety of BOSULIF (bosutinib) as a first-line treatment for patients with chronic phase Ph+ CML. The study enrolled 536 patients at multiple sites in North America, Asia and Europe. Patients were randomized 1:1 to receive BOSULIF 400mg or imatinib, a standard of care, for the duration of the study. The primary outcome was to show superiority of bosutinib over imatinib at 12 months by comparing MMR, or the proportion of patients in each arm whose levels of the Bcr-Abl1 kinase have dropped below 0.1%.

ABOUT BOSULIF (bosutinib)

BOSULIF (bosutinib) is an oral, once-daily, tyrosine kinase inhibitor (TKI), which inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases. BOSULIF was approved in September 2012 in the U.S. for the treatment of adult patients with Ph+ CML with resistance or intolerance to prior therapy and offers an important treatment option for these patients. In Europe, BOSULIF was granted conditional marketing authorization in March 2013 for the treatment of adult patients with Ph+ CML previously treated with one or more TKIs and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options. The current approved dose of BOSULIF is 500 mg orally once daily with food. For more information on BOSULIF resources available for healthcare professionals and patients, please visit www.BOSULIF.com (link is external).

IMPORTANT BOSULIF (bosutinib) SAFETY INFORMATION

Contraindication: Hypersensitivity to BOSULIF. Anaphylactic shock occurred in less than 0.2% of treated patients.

Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and abdominal pain can occur. In the clinical trial, median time to onset for diarrhea was 2 days, median duration was 1 day, and median number of episodes per patient was 3 (range 1-221). Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary.

Myelosuppression: Thrombocytopenia, anemia, and neutropenia can occur. Perform complete blood counts weekly for the first month and then monthly or as clinically indicated. Withhold, dose reduce, or discontinue BOSULIF as necessary.

Hepatic Toxicity: Twenty percent of patients experienced an increase in either ALT or AST. Liver enzyme elevation usually occurs early in treatment. Perform hepatic enzyme tests monthly for the first 3 months and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Drug-induced liver injury has occurred. Withhold, dose reduce, or discontinue BOSULIF as necessary. In patients with mild, moderate, or severe hepatic impairment, the recommended starting dose is 200 mg daily.

Renal Toxicity: An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF. Monitor renal function at baseline and during therapy, with particular attention to patients with preexisting renal impairment or risk factors. Consider dose adjustment in patients with baseline and treatment emergent renal impairment. The recommended starting doses for patients with severe renal impairment (CrCL <30 mL/min) or moderate renal impairment (CrCL 30-50 mL/min) are 300 mg and 400 mg daily, respectively.

Fluid Retention: Fluid retention can occur and may cause pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary.

Embryofetal Toxicity: BOSULIF may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised of potential hazard to the fetus and to avoid becoming pregnant while receiving BOSULIF.

Adverse Reactions: The most common adverse reactions observed in greater than 20% of patients in the Phase 1/2 safety population (N=546) were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. The most common Grade 3/4 adverse reactions and laboratory abnormalities observed in greater than 10% of patients were thrombocytopenia, anemia, and neutropenia.

CYP3A Inhibitors and Inducers: Avoid concurrent use with strong or moderate CYP3A inhibitors or inducers.

Proton Pump Inhibitors: Consider using short-acting antacids or H2 blockers instead of PPIs to avoid a reduction in BOSULIF exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.

Nursing Mothers: Given the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or BOSULIF, taking into account the importance of the drug to the mother.

Please see full Prescribing Information at www.bosulif.com (link is external).

On December 5, 2016 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported study findings demonstrating that KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, achieved an overall response rate (ORR) of 41 percent (n=7/17) (90% CI, 21-64) with follow-up of up to 27 months in patients with relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL), a type of non-Hodgkin lymphoma, who were ineligible for or failed to respond to autologous stem-cell transplantation (ASCT) (Press release, Merck & Co, DEC 5, 2016, View Source [SID1234516929]). In patients treated with KEYTRUDA, 86 percent of responses (n=6/7) were ongoing at the time of analysis with the median duration of response not yet reached (range: 2 to 23 months). These updated findings, from the ongoing phase 1b KEYNOTE-013 study, will be presented today at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego (Abstract #619). Preliminary findings from this cohort were first presented at the 2015 ASH (Free ASH Whitepaper) Annual Meeting.

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"For patients with primary mediastinal large B-cell lymphoma who are ineligible for, or fail to respond to, autologous stem-cell transplantation, the prognosis is very poor and there are limited treatment options," said Pier Luigi Zinzani, M.D., Ph.D., associate professor of hematology, Institute of Hematology "L. e A. Seràgnoli," University of Bologna. "Based on the rarity of this type of blood cancer, clinical research has been historically limited, and it’s encouraging to see clinical trials conducted in this disease where we are seeing durable responses with KEYTRUDA."

"We are committed to studying immuno-oncology approaches across a broad spectrum of cancers, including studies in more than 20 hematological subtypes," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "These data continue to support the efficacy and safety profile of KEYTRUDA in primary mediastinal large B-cell lymphoma and the importance of ongoing evaluation in this patient population."

The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in nearly 400 clinical trials, including more than 200 trials that combine KEYTRUDA with other cancer treatments. For hematologic malignancies specifically, Merck is conducting broad immuno-oncology research assessing the role of monotherapy and combination regimens with KEYTRUDA. The hematology program includes nearly 40 ongoing studies – including company sponsored, investigator sponsored and collaborative studies; several of these are registration-enabling trials.

Additional Results from KEYNOTE-013 Presented at ASH (Free ASH Whitepaper)

KEYNOTE-013 is an ongoing, multi-center, non-randomized, phase 1b trial of approximately 200 patients evaluating the safety, tolerability, and efficacy of KEYTRUDA monotherapy in patients with blood cancers, including myelodysplastic syndromes, multiple myeloma, classical Hodgkin lymphoma, PMBCL and certain other non-Hodgkin’s lymphomas (or lymphomata).

These findings are from a cohort of patients with relapsed or refractory PMBCL who were ineligible for or failed to respond to ASCT. The median age was 30.5 years (range: 22 to 62 years). Thirty-three percent of patients had failed prior autologous stem-cell replacement therapy (n=6/18) and 67 percent (n=12/18) were transplant ineligible. The co-primary endpoints of the study were ORR and safety; secondary endpoints included duration of response and complete remission rate. Patients were initially treated with KEYTRUDA as monotherapy (10 mg/kg every two weeks) which was later changed by protocol amendment to a fixed dose (200 mg every three weeks). Seventeen patients were included in the efficacy analysis.

KEYTRUDA demonstrated an ORR of 41 percent (n=7/17) (90% CI, 21-64), as assessed by International Harmonization Project Response Criteria, with a complete remission rate of 12 percent (n=2/17) (90% CI, 2-33) and a partial remission rate of 29 percent (n=5/17) (90% CI, 12-52). Additionally, 81 percent of patients (n=13/16) had reduction in target lesions. The median duration of follow-up was 11 months (range: 3 to 27 months). At the time of analysis, 86 percent of responses were ongoing (n=6/7) with the median duration of response not yet reached (range: 2 to 23 months). Two patients reached the maximum two years of treatment and remain in remission (follow-up: 25.4 months, 23.8 months).

Treatment-related adverse events were consistent with previously reported safety data for KEYTRUDA (pembrolizumab). The most common treatment-related adverse events were decreased appetite (n=2), diarrhea (n=2), fatigue (n=2), hypothyroidism (n=2), nausea (n=2), and pyrexia (n=2). Grade 3 treatment-related adverse events included neutropenia (n=1) and veno-occlusive liver disease (n=1). Immune-related adverse events included aggravated diarrhea (n=1) and radiation pneumonitis (n=1), both grade 2. There were no discontinuations or treatment-related deaths due to adverse events.

About Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

PMBCL is a rare subtype of diffuse large B-cell lymphoma (a type of non-Hodgkin lymphoma) that arises in the thymus. PMBCL affects young adults in their thirties and forties and has a slight female predominance. It accounts for five to seven percent of all aggressive lymphomas and two to three percent of all non-Hodgkin lymphomas.

About KEYTRUDA (pembrolizumab)

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 administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA 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 (pembrolizumab) 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.

In metastatic NSCLC, 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.

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.

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 (pembrolizumab) 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. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) 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 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. 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 (pembrolizumab) 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.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, 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.

In KEYNOTE-006, 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 KEYNOTE-002, 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 maculopapular 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.

KEYTRUDA 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%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

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, 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 nearly 400 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.

On December 5, 2016 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported final results from a Phase 2 clinical study of the investigational drug candidate Pracinostat and azacitidine in elderly patients with acute myeloid leukemia (AML) who were not eligible for induction chemotherapy, including evidence of prolongation of survival in the overall population and across a number of patient subgroups (Press release, MEI Pharma, DEC 5, 2016, View Source [SID1234516928]).

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In an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Saturday, Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, principal investigator of the study, reported a median overall survival of 19.1 (95%CI: 10.7-26.5) months, one-year survival of 62% and a complete response (CR) rate of 42%.

"The results from this study of Pracinostat and azacitidine in elderly patients deemed unfit for intensive therapy are particularly encouraging," said Dr. Garcia-Manero. "Despite recent advances in the treatment of AML, options for these elderly unfit patients remain limited. The combination of Pracinostat and azacitidine appears to show a long-term survival benefit in this population, including an unprecedented two-year survival rate of 41% in this study. Furthermore, the prolongation of survival over what is generally expected for azacitidine alone is observed not only in the overall population, but across virtually every defined patient subset, including cytogenetic risk group, de novo or secondary AML, age and ECOG performance status."

A copy of the presentation, entitled "A Phase 2 Study of Pracinostat and Azacitidine in Elderly Patients with Acute Myeloid Leukemia (AML) Not Eligible for Induction Chemotherapy: Response and Long-Term Survival Benefit," is available at www.meipharma.com.

The open-label Phase 2 study enrolled a total of 50 patients at 15 centers across the U.S. Median age in the study was 75 years. Patients received 60 mg of Pracinostat orally three times a week for three weeks followed by one week of rest and 75 mg m2 of azacitidine via subcutaneous injection or intravenous infusion for the first seven days of each 28-day cycle. The combination of Pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia.

Site recruitment is ongoing for the global Phase 3 study of Pracinostat and azacitidine in newly diagnosed AML patients who are ≥75 years of age or unfit for intensive induction chemotherapy.

About Pracinostat
Pracinostat is a potential best-in-class, oral histone deacetylase (HDAC) inhibitor. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for Pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive licensing, development and commercialization agreement for Pracinostat in AML and other potential indications. The deal provides the complementary resources from both organizations to rapidly advance Pracinostat into Phase 3 clinical development and expand into additional indications, including high and very high risk myelodysplastic syndrome (MDS).

Pracinostat is an investigational agent and is not approved for use in the U.S.

About AML
Acute myeloid leukemia (also known as acute myelogenous leukemia) is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 20,830 new cases of AML per year in the U.S., with an average age of about 67 years. Treatment options for AML remain virtually unchanged for nearly 40 years. Front line treatment consists primarily of chemotherapy, while the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend hypomethylating agents azacitidine or decitabine as low intensity treatment options for AML patients over the age of 60 who are unsuitable for induction chemotherapy.