On May 23, 2017 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved a new indication for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy (Press release, Merck & Co, MAY 23, 2017, View Source [SID1234519272]). KEYTRUDA is now indicated for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
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.

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The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

The recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children, the recommended dose of KEYTRUDA is 2 mg/kg (up to a maximum of 200 mg) administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Immune-mediated adverse reactions occurred with KEYTRUDA including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, KEYTRUDA (pembrolizumab) should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Monitor patients for signs and symptoms of infusion-related reactions; 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. Female patients of reproductive potential should be advised of the potential hazard to a fetus. For more information regarding immune-mediated adverse reactions, please read the additional Selected Safety Information below.

"The FDA’s approval of this new indication for KEYTRUDA further supports Merck’s commitment to helping people with difficult-to-treat cancers," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "We are thankful to the researchers, as well as the patients and their families who helped make today’s approval possible."

Further details will be included in a news release to follow.

Selected Important Safety Information for KEYTRUDA (pembrolizumab) Injection 100 mg

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 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 (pembrolizumab) 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. 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. These immune-mediated reactions may involve any organ system. 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 (pembrolizumab) 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. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, 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.

Most common adverse reactions (reported in ≥20% of patients) were fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea.

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.

On May 23, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported that the independent Data Safety Monitoring Board (DSMB) of the UNITY-CLL Phase 3 trial has successfully completed a pre-specified interim analysis to assess the contribution of TG-1101 (ublituximab) and TGR-1202 in the combination regimen of TG-1101 plus TGR-1202 (Press release, TG Therapeutics, MAY 23, 2017, View Source [SID1234519270]).

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In conducting the analysis, the DSMB reviewed efficacy data from approximately 50 patients per arm in the UNITY-CLL study who were eligible for at least one response evaluation. Based on the overall response rate data available, and in accordance with the statistical analysis plan in the study’s Special Protocol Assessment (SPA), the DSMB determined that contribution has been established and recommended the Company cease enrollment into the single agent arms. Accordingly, the study will now continue enrollment in a 1:1 ratio to only the two combination arms: the investigational arm of TG-1101 (ublituximab) plus TGR-1202 and the control arm of obinutuzumab plus chlorambucil. Additionally, the DSMB reviewed safety data from all patients on study (n > 270) as of the data cut-off date, including patients with both treatment naive and relapsed/refractory Chronic Lymphocytic Leukemia (CLL), and again identified no safety concerns in any treatment group (treatment naïve or previously treated) and recommended the continuation of the study without modification.

"We are extremely pleased that the DSMB has once again found no safety concerns that would require modifying the study. This is particularly comforting when we consider that the safety population now includes over 60 front-line CLL patients treated for more than 6 weeks with TGR-1202 alone or in combination with TG-1101. As most who have followed this area will recall, treatment naïve CLL patients appear to be exquisitely sensitive to the autoimmune mediated side effects of idelalisib, with approximately 50% experiencing Grade 3/4 liver toxicity by week 6 in a published study," stated Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer. Mr. Weiss continued, "We are also very pleased that, in accordance with our SPA, the DSMB has determined that contribution has been adequately demonstrated, enabling us to eliminate the single agent arms from continued enrollment. We are also excited to report that we continue to see strong interest in the study and enrollment remains robust. We continue to view the demand for this study as a strong indication of the need for alternative treatments for patients with CLL, even in the front-line setting. Given the current rate of enrollment, we are now targeting complete enrollment by year end, ahead of our previous guidance, which would put us in a position to report pivotal Overall Response Rate (ORR) data in the third quarter of 2018."

ABOUT UNITY-CLL PHASE 3 TRIAL

UNITY-CLL is a Global Phase 3 randomized controlled clinical trial in patients with Chronic Lymphocytic Leukemia (CLL) that includes two key objectives: first, to demonstrate contribution of each agent in the TG-1101 + TGR-1202 regimen, and second, to demonstrate superiority in Progression Free Survival (PFS) over the standard of care to support the submission for full approval of the combination. In addition, upon completion of enrollment, this trial will evaluate Overall Response Rate (ORR) for accelerated approval. The study initially randomized patients into four treatment arms: TG-1101 plus TGR-1202, TG-1101 single agent, TGR-1202 agent, and an active control arm of obinutuzumab plus chlorambucil. Pursuant to the Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA), an early interim analysis was conducted to assess contribution of each single agent which, upon success, allowed for early termination of both single agent arms.

On May 23, 2017 Sophiris Bio Inc. (NASDAQ: SPHS) (the "Company" or "Sophiris"), a late stage clinical biopharmaceutical company developing topsalysin (PRX302) for the treatment of patients with urological diseases, reported that it has received the regulatory clearance for the diluent – the medium in which topsalysin is diluted (Press release, Sophiris Bio, MAY 23, 2017, View Source [SID1234519269]). Clinical sites can now begin dosing eligible patients in a Phase 2b study in localized prostate cancer.

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On May 23, 2017 Debiopharm International SA (Debiopharm – www.debiopharm.com), part of Debiopharm Group, a Switzerland-based biopharmaceutical company, and ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that Debiopharm has acquired ImmunoGen’s IMGN529/DEBIO 1562, a clinical-stage anti-CD37 ADC for the treatment of patients with B-cell malignancies, such as non-Hodgkin lymphomas (NHL) (Press release, ImmunoGen, MAY 23, 2017, View Source [SID1234519268]).

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This Smart News Release features multimedia. View the full release here: View Source

Under the terms of the agreement, ImmunoGen received a $25 million upfront payment for IMGN529/DEBIO 1562 and is entitled to a $5 million milestone payment to be paid after completion of the transfer of ImmunoGen technologies related to the asset, which the parties expect to achieve by the end of 2017. In addition, ImmunoGen is eligible for a second success-based milestone payment of $25 million upon IMGN529/DEBIO 1562 entering a Phase 3 clinical trial.

"The purchase of IMGN529/DEBIO 1562 from a pioneer in the field of ADCs represents a strategic investment leveraging our expertise and track record in Oncology and supports our strong commitment to deliver targeted therapies and precision medicines to help patients suffering from severe diseases," stated Bertrand Ducrey, CEO of Debiopharm.

"IMGN529/DEBIO 1562 has already generated compelling clinical data and we look forward to further exploring it in combination with Rituxan, which could provide an attractive alternative to conventional chemotherapies for patients with NHL such as diffuse large-cell B-cell lymphoma (DLBCL)," said Chris Freitag, vice president of clinical research and development of Debiopharm.

IMGN529/DEBIO 1562 demonstrated evidence of anticancer activity in NHL in a Phase 1 monotherapy trial and successfully completed a safety run-in study in combination with Rituxan. The product is now ready to move forward into a Phase 2 trial in NHL, and particularly in DLBCL for which it has Orphan Drug status.

"With a strong history of developing and bringing oncology drugs to market, Debiopharm offers the right mix of resources and capabilities to advance IMGN529/DEBIO 1562 through its next phase of development," stated Mark Enyedy, president and chief executive officer of ImmunoGen. "Consistent with the strategic review of our portfolio undertaken last fall, this transaction further enables us to prioritize our development efforts on mirvetuximab soravtansine and our IGN programs, while generating near-term value from IMGN529/DEBIO 1562."

On May 23, 2017 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that abstracts highlighting progress in the rucaparib clinical development program will be presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 2-6 in Chicago (Press release, Clovis Oncology, MAY 23, 2017, View Source [SID1234519267]).

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Four abstracts highlighting ongoing rucaparib clinical trials will showcase some of the multiple cancer types in which the compound is being studied, including germline and somatic BRCA-mutated, relapsed, high-grade ovarian cancer; metastatic castration-resistant prostate cancer associated with homologous recombination deficiency; and HER2 negative metastatic breast cancer.

"The abstracts being presented at ASCO (Free ASCO Whitepaper) 2017 highlight the depth of our clinical program exploring the potential of rucaparib as a precision medicine therapeutic for multiple cancer types," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "The oncology community has taken great interest in PARP inhibitors and the role of these novel therapeutics within the cancer treatment paradigm. We are pleased to describe these current clinical studies evaluating rucaparib in various solid tumor settings at this prestigious meeting, and importantly, we look forward to announcing the top-line results from ARIEL3 in the ovarian cancer maintenance treatment setting by the end of June."

Rucaparib is Clovis Oncology’s oral, potent, small-molecule inhibitor of PARP1, PARP2 and PARP3. In December 2016, the FDA approved rucaparib (Rubraca) tablets as monotherapy for women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a deleterious BRCA mutation (germline and/or somatic) as identified by an FDA-approved companion diagnostic test.

The ARIEL3 pivotal study of rucaparib is a randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance treatment to platinum-sensitive ovarian cancer patients can extend the period of time for which the disease is controlled after a response to platinum-based chemotherapy. Top-line results from ARIEL3 are anticipated by the end of June, and the Company plans to provide a more comprehensive presentation of the ARIEL3 results in a scientific session at a medical meeting later this year. Pending positive data, the Company intends to submit a supplemental New Drug Application (NDA) for a second line or later maintenance treatment indication within approximately four months of the database lock.

The three trials-in-progress abstracts accepted for presentation at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting comprise:

Abstract TPS5603 (Poster #423b) – ARIEL4: An International, Multicenter Randomized Phase 3 Study of the PARP Inhibitor Rucaparib vs Chemotherapy in Germline or Somatic BRCA1- or BRCA2-Mutated, Relapsed, High-Grade Ovarian Carcinoma

Presenter: Amit M. Oza, MD, Princess Margaret Cancer Centre, University Health Network
Session: Gynecologic Cancer
Date/Time: Saturday, June 3, 1:15-4:45 p.m. CDT
Location: Hall A
Abstract TPS1117 (Poster #103b) – An open-label, phase II study of rucaparib, a PARP inhibitor, in HER2 negative metastatic breast cancer patients with high genomic loss of heterozygosity: RUBY.

Presenter: Anne Patsouris, MD, Institute of West Cancerology Paul Papin
Session: Breast Cancer-Metastatic
Date/Time: Sunday, June 4, 8:00-11:30 a.m. CDT
Location: Hall A
Abstract TPS5087 (Poster #160b) – Trial of RucaparIb in ProsTate IndicatiONs 3 (TRITON3): An International, Multicenter, Randomized, Open-Label Phase 3 Study of Rucaparib vs Physician’s Choice of Therapy for Patients (Pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Associated with Homologous Recombination Deficiency (HRD)

Presenter: Charles J. Ryan, MD, University of California San Francisco Helen Diller Family Comprehensive Cancer Center
Session: Genitourinary (Prostate) Cancer
Date/Time: Monday, June 5, 1:15-4:45 p.m. CDT
Location: Hall A
Additionally, Clovis’ companion diagnostics collaborator Foundation Medicine will present results from a genomic-profiling study:

Abstract 5512 (Oral #5512) – Comprehensive genomic profiling (CGP) with loss of heterozygosity (LOH) to identify therapeutically relevant subsets of ovarian cancer (OC)

Presenter: Julia Andrea Elvin, MD PhD, Foundation Medicine, Inc.
Session: Clinical Science Symposium
Date/Time: Monday, June 5, 8:48-9:00 a.m. CDT
Location: E450ab
Clovis’ rucaparib posters will be available online at View Source as of the time they are presented at the meeting.

About Rucaparib

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. The MAA submission in Europe for an ovarian cancer treatment indication was submitted and accepted during the fourth quarter of 2016. Additionally, rucaparib is being developed as maintenance treatment for ovarian cancer in the ARIEL3 trial for patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA, as well as biomarker negative patients. Topline results from ARIEL3 are expected by late June, which, pending positive data, is expected to be followed by the submission of a sNDA for a second line or later maintenance treatment indication. Rucaparib is also being developed in patients with mutant BRCA tumors and other DNA repair deficiencies beyond BRCA – commonly referred to as homologous recombination deficiencies, or HRD. Studies open for enrollment or under consideration include prostate, breast, pancreatic, gastroesophageal, bladder and lung cancers. Clovis holds worldwide rights for rucaparib.