On August 25, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported The New England Journal of Medicine has published data from the Phase III CASTOR (MMY3004) study of daratumumab (Press release, Genmab, AUG 25, 2016, View Source [SID:1234514714]). The CASTOR data were presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). Daratumumab was granted a Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) based on these data in July 2016. Schedule your 30 min Free 1stOncology Demo! The Phase III CASTOR study included 498 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with subcutaneous bortezomib (a type of chemotherapy, called a proteasome inhibitor) and dexamethasone (a corticosteroid), or bortezomib and dexamethasone alone. The study met the primary endpoint of improving progression free survival (PFS); Hazard Ratio (HR) = 0.39, p<0.001. The median PFS for patients treated with daratumumab has not been reached, compared to median PFS of 7.2 months for patients who did not receive daratumumab. The overall response rate was 82.9% for patients treated with daratumumab versus an overall response rate of 63.2% in the group that did not receive daratumumab. The rate of very good partial response or better was also higher for the group treated with daratumumab (59.2% vs 29.1%). The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with bortezomib and dexamethasone compared to those who only received bortezomib and dexamethasone were thrombocytopenia (45.3% vs 32.9%), anemia (14.4% vs 16.0%) and neutropenia (12.8% vs 4.2%). Daratumumab-associated infusion-related reactions were reported in 45.3% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. This is consistent with the reported safety profile of daratumumab monotherapy and background bortezomib/dexamethasone therapy.
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"We are pleased that the positive data from the Phase III CASTOR study of daratumumab, which was presented earlier this year at the ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) meetings, has now been published in the prestigious New England Journal of Medicine," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "The data from this study formed part of the basis of this month’s submission of the supplemental Biologics License Application to the U.S. Food and Drug Administration and the submission of the variation to the Marketing Authorization to the European Medicines Agency."
About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6
About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,8 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,8 antibody-dependent cellular phagocytosis9,10 and antibody-dependent cellular cytotoxicity.7,8 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.7,11
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.
Author: [email protected]
Biothera Pharmaceuticals Expands Relationship with Merck, Enters Collaboration for Combination Cancer
On August 24, 2016 Biothera Pharmaceuticals, Inc. reported a collaboration with Merck, known as MSD outside the United States and Canada, to expand the companies’ ongoing clinical program evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 inhibitor, in combination with Biothera’s Imprime PGG, a Pathogen Associated Molecular Patterning molecule, or PAMP (Press release, Biothera Pharmaceuticals, AUG 24, 2016, View Source [SID1234562109]). Imprime PGG acts as an immunological "ignition switch" enlisting the innate immune system to enhance the therapeutic efficacy of tumor targeting, anti-angiogenic, and immune checkpoint inhibitor antibodies.
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Under this new collaboration, a Phase 2 clinical trial is anticipated to enroll up to 95 patients who have either advanced melanoma no longer responding to initial treatment with a checkpoint inhibitor therapy or TNBC whose disease has progressed following treatment with one or more lines of therapy for metastatic disease. Biothera will be the sponsor of the study, which is planned to begin in the fourth quarter of 2016. Merck will provide clinical supplies of KEYTRUDA for the planned studies. Other terms of the collaboration were not disclosed.
Biothera previously announced an agreement in December 2015 for Merck to supply KEYTRUDA for a Phase 1b/2 clinical study testing combination therapy with Imprime PGG in NSCLC patients. The Big Ten Cancer Research Consortium will conduct the multi-center trial, which is expected to commence this fall.
Barry Labinger, Chief Executive Officer of Biothera, stated, "Combination therapies with breakthrough medicines such as KEYTRUDA are potentially the next major advance in the treatment of cancer. We believe that Imprime PGG is uniquely suited to complement immune checkpoint inhibitor therapy and meaningfully enhance patient outcomes. The trial will assess safety and efficacy, as well as provide biomarker and pharmacodynamic data that will inform the design of potential Phase 3 pivotal studies."
Eric Rubin, M.D., Vice President and Therapeutic Area Head, Oncology Early-stage Development, Merck Research Laboratories, commented, "As a leading innovator in the field of immuno-oncology, Merck is dedicated to advancing breakthrough science by continuing to identify novel combinations with potential to improve the care for people with cancer. We are pleased to expand our partnership with Biothera as we explore the potential for combining KEYTRUDA with their lead candidate."
BeiGene Appoints Amy Peterson, M.D. as Chief Medical Officer, Immuno-oncology
On August 24, 2016 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company focused on developing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the appointment of Amy C. Peterson, M.D. as Chief Medical Officer, Immuno-oncology (Press release, BeiGene, AUG 24, 2016, View Source;ut=1472118472&p=RssLanding&cat=news&id=2197224 [SID:1234514748]). Dr. Peterson will lead the global clinical development of BGB-A317, BeiGene’s PD-1 inhibitor; BGB-290, BeiGene’s PARP inhibitor; and the expanding pipeline of other immuno-oncology agents expected to enter clinical development. Dr. Eric Hedrick, currently serving as the Interim Chief Medical Officer, will continue to oversee global clinical hematology development including the program for BGB-3111, BeiGene’s BTK inhibitor, and will remain serving as an advisor as BeiGene continues to expand its global clinical development capabilities.
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"We are delighted to have Dr. Peterson join our team," said John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene. "BeiGene continues to expand its senior medical leadership in response to emerging global development opportunities, particularly in immuno-oncology. Amy’s broad experience in oncology drug development and her academic background in immuno-oncology research are well-suited to our expanding clinical development efforts. We very much look forward to her contribution in the continued growth and development of our existing and future pipeline and the company as a whole."
"BeiGene has a robust pipeline of clinical stage, internally discovered molecules against validated targets as well as an expanding roster of candidates in the preclinical pipeline," said Dr. Peterson. "I look forward to leveraging my past experiences to successfully build an organization that can bring these assets to market while continuing to expand the clinical pipeline."
Prior to joining BeiGene, Dr. Peterson was Vice President of Clinical Development at Medivation, where she was primarily responsible for the development of enzalutamide and talazoparib in breast cancer and of pidilizumab in diffuse large b-cell lymphoma. Previously, she served as Associate Group Medical Director at Genentech, where she was responsible for the development of early stage molecules targeting multiple major pathways in oncology. Prior to joining Genentech, Dr. Peterson was an Instructor of Medicine in Oncology at the University of Chicago, where she conducted translational research in tumor immunology in conjunction with Dr. Thomas F. Gajewski.
Dr. Peterson received her M.D. from Thomas Jefferson University in Philadelphia, PA, and she completed her residency in Internal Medicine at Northwestern Memorial Hospital and Fellowship in Hematology and Oncology at the University of Chicago. She holds a Bachelor of Arts degree from Wesleyan University in Middletown, CT.
New England Journal of Medicine Publishes MINDACT Trial Results Proving the Clinical Utility of MammaPrint® in Assisting Physicians to Identify Early-Stage Breast Cancer Patients who can Safely Forgo Chemotherapy
On August 24, 2016 Agendia, Inc., a world leader in personalized medicine and molecular cancer diagnostics, reported the peer-reviewed publication of the primary outcome results of the Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy (MINDACT) clinical trial in the prestigious New England Journal of Medicine (NEJM) (Press release, Agendia, AUG 24, 2016, View Source [SID:1234514712]). [i, iii, iv] The publication demonstrates that 46% of breast cancer patients considered for chemotherapy, whose tumors are classified MammaPrint Low Risk, have excellent survival without chemotherapy, and can thus be candidates to avoid this toxic therapy. [i, pg. 717]
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MINDACT is a collaboration between Agendia, the European Organization for Research and Treatment of Cancer (EORTC) and the Breast International Group (BIG). A unique phase III prospective, randomized, controlled study of 6,693 patients across 112 European cancer centers, MINDACT provides the highest level of clinical evidence (Level 1A) and confirms the clinical utility of using Agendia’s MammaPrint 70-gene breast cancer recurrence assay to help predict clinical outcome in women with early-stage breast cancer.
"When we developed MammaPrint, we knew we wanted to achieve the same level of evidence required for a typical pharmaceutical drug. That is why we are one of only a few diagnostic tests with FDA clearance and why we rigorously evaluated MammaPrint in the context of clinical-pathological factors in the randomized MINDACT trial," said Prof. Laura van ’t Veer, Chief Research Officer at Agendia, and Leader, Breast Oncology Program, and Director, Applied Genomics at UCSF Helen Diller Family Comprehensive Cancer Center. "Now indeed, we have the only genomic assay with Level 1A evidence to help physicians more accurately predict risk of distant metastasis in patients with early-stage breast cancer."
MINDACT is the first prospective translational clinical study of this magnitude in early-stage breast cancer to report the results of its primary objective and publish them in a peer-reviewed journal. At 5 years, patients who did not receive adjuvant chemotherapy but were classified as being at high risk for breast cancer recurrence based on clinical-pathological factors and as being at Low Risk based on MammaPrint, had similar rates of disease free survival. [i, pg. 717]
"The design of the MINDACT trial proves the clinical utility of the MammaPrint assay," said Dr. Gabriel Hortobagyi, MD, FACP, FASCO Professor and Chair Emeritus of the Department of Breast Medical Oncology at the MD Anderson Cancer Center (MDACC) and Chair of the Agendia Inc. Medical Advisory Board. "The reporting of these conclusive results of the trial will now give physicians increased confidence that in using MammaPrint, their treatment decisions will be based on the highest level of clinical evidence and will minimize the incidence of over- or under-treatment."
"We understand that a risk–benefit assessment and decisions with respect to the use of adjuvant chemotherapy are highly variable and personalized among physicians and individual patients. However, these findings provide clinical utility by demonstrating that MammaPrint’s accuracy in helping to detect patients with a low risk of distant recurrence could be safely used in the management of over one hundred thousand[ii] women and potentially spare them from unnecessary chemotherapy," said Dr. William Audeh, Chief Medical Officer at Agendia. "The toxicities and side effects of chemotherapy may outweigh the potentially small and non-statistically significant benefit (1.5% 95% CI, 0.50 to 1.21; p = 0.27) of chemotherapy in women at high risk based on clinical factors but at Low Risk per MammaPrint. Thus, physicians and breast cancer patients may on an individual basis decide to avoid it."
In MINDACT, when the authors looked at the patients with the most common type of breast cancer, hormone receptor positive, human epidermal growth factor receptor 2 negative, and lymph node negative (HR+/HER2-/LN0) disease, 75% were identified as having a Low Risk of recurrence using MammaPrint. The Distant Metastasis Free Interval (DMFI) for these patients (which according to the researchers is the optimal endpoint to evaluate a genomic assay that looks at prognosis and benefit of chemotherapy treatment) was 97.8% without chemotherapy. [i, supplement pg. 12-13]
In MINDACT, this MammaPrint Low Risk group of breast cancer patients who may be candidates to forgo chemotherapy is over four times larger than the proportion identified with a low-Recurrence Score (RS) in both TAILORx.[v] and Plan B.[vi]. The TAILORx trial, which is the trial that would validate the appropriate cut-offs for the Oncotype DX 21-gene breast cancer recurrence assay, has only reported data on the low risk arm of the study that included 15% of the patients who are in the non-randomized arm of patients with RS 10 and under. The TAILORx trial, has not presented results of its primary objective of the outcome of patients with RS between 11-25.
"MINDACT provides us with the highest level of evidence to support what we at Agendia have always believed, that MammaPrint is a definitive, accurate and clinically relevant breast cancer recurrence assay. The quality of life and cost efficiency implications of helping physicians choose the appropriate management for women with breast cancer is the reason we do what we do every day," commented Mark Straley, Chief Executive Officer, Agendia. "We understand that ultimately, the decision to receive or forgo chemotherapy lies with each patient and physician who is properly informed about the potential side effects and benefits of such treatment. Nonetheless, MammaPrint could potentially change the standard of care and we look forward to its recommendation for inclusion in all early-stage breast cancer management guidelines. This will ensure that even more patients, physicians and healthcare systems are aware of the benefits of MammaPrint-based management decisions."
Breast cancer is the most frequently diagnosed cancer in women worldwide.[vii] In 2012, there were nearly 1.7 million new breast cancer cases among women worldwide, accounting for 25% of all new cancer cases in women.[viii] MINDACT initial results were selected for a prestigious breakthrough presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2016, 16-20 April.
For more information on the MINDACT trial publication, please visit the Agendia newsroom: View Source
[i] Cardosa F, van’t Veer LJ, Bogaerts J et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med 2016; 375: 717-29.
[ii] Based on applying MINDACT risk data to: American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. (online) and American Cancer Society. Breast Cancer Facts & Figures 2015-2016. Atlanta: American Cancer Society, Inc. 2015.
[iii] Hudis CA, Dickler, M. Increasing Precision in Adjuvant Therapy for Breast Cancer. N Engl J Med 2016; 375: 790-91.
[iv] For disclosures regarding involvement in trial, see page 728 of publication (Cardosa F. NEJM 2016) mentioned above.
[v] Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 2015; 373: 2005-14.
[vi] Gluz O, Nitz, U. A., Matthias, C, et al. West German Study Group Phase III Plan B Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. J Clin Oncol 2016; 34(20):2341-9
[vii] World Health Organization. Breast cancer: prevention and control. Website. View Source Accessed March 2016.
[viii] American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. (online)
About MINDACT
MINDACT is a prospective, randomized, phase III, controlled clinical trial that investigates the clinical utility of MammaPrint, when used in conjunction with standard clinical pathological criteria, for the selection of patients unlikely to benefit from adjuvant chemotherapy. From 2007 to 2011, 6,693 women who had undergone surgery for early-stage breast cancer enrolled in the trial, across 112 centers in nine countries. Patients were categorized as low or high risk for tumor recurrence in two ways: first, through analysis of tumor tissue using MammaPrint; and second, using Adjuvant! Online, a tool that calculates risk of breast cancer recurrence based on common clinical pathological factors. Patients characterized in both clinical and genomic assessments as low risk are spared chemotherapy, while patients characterized as high risk are advised chemotherapy. Those with discordant results were randomized to use either clinical or genomic risk (MammaPrint) evaluation for chemotherapy treatment.
MINDACT is a population based trial. A risk–benefit assessment and decisions with respect to the use of chemotherapy are highly variable among physicians and patients, and even national and international guidelines differ in their recommendations. Ultimately, the decision to receive or forgo chemotherapy (or any other treatment) lies with each patient who is properly informed about the potential side effects and the potential benefits of such treatment. For the same risk–benefit scenario, different patients may make different decisions. [i, pg. 727-28]
About MammaPrint
MammaPrint is a FDA-cleared in vitro diagnostic test, performed in a single laboratory, using the gene expression profile of breast cancer tissue samples to assess a patients’ risk for distant metastasis. The MammaPrint result is indicated for use by physicians as a prognostic marker only, along with other clinical-pathological factors. MammaPrint is not intended for diagnosis, or to predict or detect response to therapy, or to help select the optimal therapy for patients. Results should be taken in the context of other relevant clinical-pathological factors and standard practice of medicine.
Cantargia AB: Cantargia Interim Report January – June 2016
On August 24, 2016 Cantargia AB ("Cantargia") reported its interim report for January – June 2016 is available on the company website (www.cantargia.com/Investors/Reports) (Press release, Cantargia, AUG 24, 2016, View Source [SID:1234514711]).
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Significant events in the second quarter
· The exercise period for warrants of series TO 1 and TO 3 began on 23 March 2016 and ended on 13 April 2016. In total, 4,127,260 warrants of both series were exercised, representing around 83.5 per cent of the number of warrants issued. Through the warrants Cantargia raised approximately SEK 31.4 million before issue costs.
· During the period the Company gave investor presentations at the international BioEquity conference in Copenhagen on 10 May 2016 and at the Småbolagsdagen small cap investor event at the Sheraton Stockholm Hotel on 13 June 2016.
· The annual report for the financial year 2015 was published on 29 April 2016. The company held its Annual General Meeting on 25 May 2016 and published a report on the AGM the following day. The annual report and AGM report are available for download on the company’s website, www.cantargia.com.
· Cantargia received a Notice of Allowance from the US Patent Office for IL1RAP as target molecule for antibody-based treatment in acute lymphoblastic leukemia followed by a Notice of Allowance for IL1RAP as target molecule for antibody-based treatment in solid tumours from the same patent office. The company also received formal approval in Japan of a patent for solid tumours.
· The company announced that its CAN04 product candidate has been shown to have a high level safety in high doses – repeated treatment with up to 100 mg/kg. During the period Cantargia also decided that the company will conduct further process development studies to establish a strong foundation for long-term production and that the start of the GLP toxicity study will therefore be postponed until autumn 2016. Consequently, the start of clinical studies will also be postponed until the end of the first quarter of 2017.
· A third party filed an opposition to Cantargia’s patent in Europe for IL1RAP as a target molecule for antibody treatment and leukemia diagnostics. Cantargia will be working with its patent agents and the European Patent Office to conduct the process in a professional and correct manner.
Significant events after the end of the period
· In July Cantargia announced that the US Patent Office had approved the company’s application for IL1RAP as target molecule for antibody-based treatment of solid tumours.
· In August Cantargia announced that the company’s former CEO, Agneta Svedberg, has exercised 1,250 warrants of series 2011/2016. The exercise of the warrants will raise SEK 250,212.50 for Cantargia.
Financial information
First half (1 Jan 2016 – 30 Jun 2016)
· Other operating revenue was kSEK 0 (0).
· Earnings after financial items were kSEK -16,023 (-9,059).
· Earnings per share were approximately SEK -0.91 (-0.68).
· The equity/assets ratio was around 87 (89) per cent compared with the beginning of the year.
Second quarter (1 Apr 2016 – 30 Jun 2016)
· Other operating revenue was kSEK 0 (0).
· Earnings after financial items were kSEK -7,926 (-5,432).
· Earnings per share were approximately SEK -0.45 (-0.41).
Definitions
· Earnings per share: Profit for the period divided by 17,633,134 shares as at 30 June 2016.
· Equity/assets ratio: Equity divided by total capital.
· Unless otherwise indicated, figures in parentheses refer the same period in the previous year.
This constitutes information that Cantargia is required to publish under the EU’s Market Abuse Regulation. The information was submitted for publication through the above contact person at 8:30 (CEST) on August 24, 2016.
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