1stOncology™: Cancer Intelligence Service – Page 16318 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Janssen’s daratumumab accepted for accelerated CHMP assessment for treatment of European patients with heavily pre-treated multiple myeloma

On September 25, 2015 Janssen-Cilag International NV reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has accepted its request for an accelerated assessment of the daratumumab Marketing Authorisation Application (MAA) (Press release, Johnson & Johnson, SEP 25, 2015, View Source [SID:1234507552]). This acceptance follows the earlier regulatory submission of a MAA which seeks authorisation of daratumumab as a single agent for the treatment of patients with relapsed and refractory multiple myeloma and is currently pending validation by the EMA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The CHMP grants accelerated assessment when a medicinal product is expected to be of major public health interest particularly from the point of view of therapeutic innovation.

Daratumumab is an investigational, human anti-CD38 monoclonal antibody that works by binding to CD38, a signalling molecule found on the surface of multiple myeloma cells.1,2,3,4 In doing so, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumour cell death through multiple immune-mediated and other mechanisms of action.5

The MAA includes data from the Phase 2 MMY2002 (SIRIUS) monotherapy study, presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper),6 and data from the Phase 1/2 GEN501 monotherapy study, recently published in The New England Journal of Medicine,7 and data from three additional supportive studies.

"Janssen is pleased with the CHMP’s acceptance of an accelerated regulatory review timeline for daratumumab, which reflects the high unmet need for new treatment options for patients with multiple myeloma, currently an incurable disease," said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. "We continue to work closely with European health authorities to make daratumumab available to these patients as soon as possible."

In July 2013 daratumumab was granted Orphan Drug Status by the EMA for the treatment of plasma cell myeloma.8 Furthermore, this step forward in Europe also follows the acceptance for Priority Review of the Biologics License Application for daratumumab with the U.S. FDA on September 4, 2015.

In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement which granted Janssen an exclusive worldwide license to develop, manufacture, and commercialise daratumumab.

About Multiple Myeloma

Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.9 MM is the second most common form of blood cancer, with around 39,000 new cases in Europe in 2012.10 MM most commonly affects people over the age of 65 and is more common in men than in women.11 Across Europe, five-year survival rates are 23 percent to 47 percent of people diagnosed.12 Almost 29 percent of patients with MM will die within one year of diagnosis.13 Although treatment may result in remission, unfortunately patients will most likely relapse as there is currently no cure. While some patients with MM 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.11 Patients who relapse after treatment with standard therapies, including proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs), have poor prognoses and few treatment options available.14

About Daratumumab

Daratumumab is an investigational human monoclonal antibody that binds with high affinity to the CD38 molecule, which is found on the surface of multiple myeloma cells. It is believed to induce rapid tumour cell death through multiple immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosic and antibody-dependent cellular cytotoxicity, as well as via induction of apoptosis.5 Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases in which CD38 is expressed, such as smouldering myeloma and non-Hodgkin lymphoma.

Oncolytics Biotech® Inc. Collaborators Present Data from Clinical Study in Multiple Myeloma

On September 25, 2015 Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC) (NASDAQ:ONCY) reported that Dr. D.W. Sborov and colleagues made a poster presentation at the 15th International Myeloma Workshop (IMW) (Press release, Oncolytics Biotech, SEP 25, 2015, View Source [SID:1234507549]). The poster presentation, entitled "Combination Carfilzomib and the Viral Oncolytic Agent REOLYSIN in Patients with Relapsed Multiple Myeloma: A Pilot Study Investigating Viral Proliferation," discloses initial findings from a pilot study (NCI-9603) in patients with relapsed or refractory multiple myeloma treated using the combination of carfilzomib and REOLYSIN. The IMW runs from September 23rd to 26th in Rome, Italy.

Highlights of the data presented include:

100% of patients (8 of 8) experienced an objective response as measured by changes in blood monoclonal protein. Of these, 2 patients had a very good partial response (VGPR), 3 patients had a partial response (PR) and 3 patients had a minor response (MR);
Only one patient has progressed to date and five of eight remain on study;
The combination of carfilzomib and REOLYSIN produced a significant (p=0.005) increase in caspase-3, a marker associated with apoptotic (programmed) cell death; and
The treatment combination was associated with an increased infiltration of CD8+ T-cells and the significant (p=0.005) upregulation of PD-L1, suggesting that the addition of a PD-1 or PD-L1 inhibitor may further optimize the treatment regimen.
"These findings demonstrate that the combination of carfilzomib and REOLYSIN shows promise in hematological malignancies like multiple myeloma and provide compelling evidence that such drug combinations promote viral replication and cancer cell death," said Dr. Matt Coffey, Chief Operating Officer of Oncolytics. "Based on these results, we intend to move into randomized studies in this indication."

The investigators noted that this is the first time a REOLYSIN-based combination has been tested in relapsed multiple myeloma patients. A previous single-agent study conducted by the collaborators in this patient population showed that REOLYSIN was well tolerated. The collaborators and others were noted to have conducted preclinical investigations that demonstrated that the combination of REOLYSIN and carfilzomib synergistically increased the killing of multiple myeloma cells. This provided the clinical rationale for this study. In this study, the combination of carfilzomib and REOLYSIN produced a significant (p=0.005) increase in caspase-3, a marker associated with apoptotic cell death. The researchers also determined that the combination of REOLYSIN and carfilzomib increases infiltration of CD8+ T-cells and significantly (p=0.005) upregulates PD-L1. The investigators concluded that these findings necessitate continued investigation, and suggest that the addition of a PD-1 or PD-L1 inhibitor may further optimize the REOLYSIN and carfilzomib regimen.

"To this point, multiple myeloma has not responded to checkpoint inhibitor therapy," said Dr. Brad Thompson, President and CEO of Oncolytics. "The combination of REOLYSIN and carfilzomib upregulates PD-L1 and increases infiltration of CD8+ T-cells, which may make the tumor sensitive to anti-PD-L1 therapy. The follow-on randomized study we are currently planning is expected to have a patient group treated with the combination of REOLYSIN, a standard of care chemotherapy, and a checkpoint inhibitor, as well as a patient group receiving REOLYSIN and a standard of care chemotherapy."

NCI-9603 is a U.S. National Cancer Institute sponsored single-arm, open-label study of intravenously administered REOLYSIN with dexamethasone and carfilzomib to patients with relapsed or refractory multiple myeloma. Patients receive treatment on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle, to be repeated in the absence of disease progression or unacceptable toxicity. Approximately 12 patients will be enrolled in the study. The primary outcomes include measuring reovirus replication, safety, and tolerability. Secondary outcomes include examining objective response, duration of response, clinical benefit, progression-free survival, and time to progression. Other outcomes will include the measurement of immunologic correlative markers.

A copy of the poster will be available on the Oncolytics website at: View Source

About Multiple Myeloma
Multiple Myeloma is a cancer of the plasma cells and the second most common hematological malignancy. The American Cancer Society estimates there will be 26,850 new cases diagnosed in the United States and 11,240 deaths from the disease in 2015.

CHMP recommends EU approval for Roche’s combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) in advanced melanoma

On September 25, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the EU Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for CotellicTM (cobimetinib), when used in combination with Zelboraf (vemurafenib), for the treatment of BRAF V600 mutation-positive unresectable or metastatic melanoma (Press release, Hoffmann-La Roche , SEP 25, 2015, View Source [SID:1234507547]). Approximately 50% of melanoma skin cancers are BRAF-positive, and more than 55,000 people worldwide die every year from melanoma.1

"Today’s CHMP positive opinion is a substantial step forward for people with BRAF-positive skin cancer in Europe and around the world," said Sandra Horning, M.D., Chief Medical Officer and Global Head of Product Development. "The Cotellic and Zelboraf combination will provide physicians with a powerful therapeutic option that can help patients live significantly longer without their disease progressing compared to Zelboraf alone."

The CHMP’s recommendation is based primarily on results of the pivotal Phase III coBRIM study. These data showed that people who received the combination of Cotellic and Zelboraf lived over a year without their disease worsening (median progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf alone; hazard ratio=0.58, 95 percent confidence interval 0.46-0.72).2 The objective response rate was also higher for the combination arm compared to Zelboraf alone (70 vs. 50 percent; p<0.0001).2 The most common adverse events in the combination arm of the pivotal study were diarrhoea, rash, nausea, fever, sun sensitivity, liver lab abnormalities, elevated creatine phosphokinase (CPK, an enzyme released by muscles) and vomiting.
Supportive data early in development from the Phase Ib BRIM7 study indicated that the combination of Cotellic and Zelboraf helped people who had not been previously treated with a BRAF inhibitor live more than two years (median overall survival 28.5 months).3

Based on this CHMP recommendation, a final decision regarding the approval of the combination of Cotellic and Zelboraf is expected from the European Commission by the end of 2015.

Cotellic recently received approval in Switzerland for use in combination with Zelboraf as a treatment for patients with advanced melanoma, and the U.S. Food and Drug Administration (FDA) is expected to make a decision on Roche’s new drug application for the combination before the end of the year.

About melanoma
Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer.4,5 A V600 mutation of the BRAF protein occurs in approximately half of melanomas, and should therefore be tested to identify the best treatment option.6 When melanoma is diagnosed early, it is generally a curable disease,7,8 but most people with advanced melanoma have a poor prognosis.5 More than 232,000 people worldwide are currently diagnosed with melanoma each year.1 In recent years, there have been significant advances in treatment for metastatic melanoma, and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.9

About Cotellic and Zelboraf in combination
Zelboraf was the first approved treatment for patients with unresectable or metastatic melanoma with BRAF V600 mutation as detected by a validated test, such as Roche’s cobas 4800 BRAF Mutation Test. Zelboraf is not indicated for use in patients with wild-type BRAF melanoma. Cotellic (cobimetinib) is designed to selectively block the activity of MEK,10 one of a series of proteins inside cells that make up the MAPK signaling pathway that helps regulate cell division and survival.11 In the majority of patients, resistance to BRAF-inhibitor monotherapy will eventually occur through re-activation of the MAPK pathway via MEK.12 Cotellic was developed to overcome resistance to BRAF-inhibition and prevent re-activation of the pathway. Cotellic binds to MEK, while Zelboraf binds to mutant BRAF, to interrupt abnormal signalling that can cause tumours to grow.13,14

Cotellic is also being investigated in combination with several investigational medicines, including immunotherapy, in several tumour types such as non-small cell lung cancer and colorectal cancer. Cotellic was discovered by Exelixis Inc. and is being developed by Roche in collaboration with Exelixis.

Array BioPharma To Hold Conference Call To Discuss Clinical Data Presentations In Melanoma And Colorectal Cancer On September 28, 2015

On September 25, 2015 Array BioPharma Inc. (Nasdaq: ARRY) reported it will hold a conference call to discuss preliminary results from two melanoma trials and a colorectal cancer trial on Monday, September 28, 2015 (Press release, Array BioPharma, SEP 25, 2015, View Source;p=RssLanding&cat=news&id=2090445 [SID:1234507544]). Ron Squarer, Chief Executive Officer, and Victor Sandor, M.D., Chief Medical Officer, will lead the call.

The trials include a Phase 2 combination trial of binimetinib and encorafenib in BRAF-mutant melanoma patients (LOGIC2), a Phase 1b/2 combination trial of binimetinib and a CDK4/6 inhibitor in NRAS-mutant melanoma patients and a Phase 2 combination trial of encorafenib and an EGFR inhibitor with or without the addition of a PI3K inhibitor in patients with BRAF-mutant colorectal cancer. Data from these trials will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s (ESMO) (Free ESMO Whitepaper) annual European Cancer Conference (ECC) or were presented at the 2015 ESMO (Free ESMO Whitepaper) World Congress of Gastrointestinal Cancer.

Conference Call Information

Date: Monday, September 28, 2015
Time: 9:00 a.m. eastern time
Toll-Free: (844) 464-3927
Toll: (765) 507-2598
Pass Code: 43837177
Webcast, including Replay and Conference Call Slides: View Source
– See more at: View Source;p=RssLanding&cat=news&id=2090445#sthash.oer1i36t.dpuf

Merck and Pfizer Announce FDA Orphan Drug Designation for Investigational Immunotherapy Avelumab in Merkel Cell Carcinoma

On September 25, 2015 Merck and Pfizer reported that the US Food and Drug Administration (FDA) has granted orphan drug designation for the investigational cancer immunotherapy avelumab* for the treatment of Merkel cell carcinoma (MCC), a rare and aggressive type of skin cancer (Press release, Merck KGaA, SEP 25, 2015, View Source [SID:1234507551]).1,2 Each year, there are approximately 1,500 new cases of MCC diagnosed in the US.3

Avelumab (also referred to as MSB0010718C) is an investigational fully human monoclonal IgG1 antibody against programmed death-ligand 1 (anti-PD-L1). Merck and Pfizer are currently conducting a Phase II study (JAVELIN Merkel 200) to assess the safety and efficacy of avelumab in patients with metastatic MCC who have progressed after at least one prior chemotherapy regimen.

"We continue to dedicate significant resources to accelerate our clinical trial program, with a goal of helping patients who are fighting rare and difficult-to-treat diseases, such as Merkel cell carcinoma," said Dr. Luciano Rossetti, Head of Global Research & Development at Merck’s biopharmaceutical business, Merck Serono. "It is encouraging to be included in the FDA’s orphan drug program as we eagerly await the results of our Phase II trial of avelumab in this deadly skin cancer."

"This is a rare and lethal type of skin cancer, especially when it has progressed despite prior chemotherapy," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology. "There is a strong scientific rationale that by harnessing the body’s immune system, we may be able to control the disease and provide hope to patients fighting Merkel cell carcinoma."

JAVELIN Merkel 200 is a multicenter, single-arm, open-label study evaluating patients with metastatic MCC who have previously received at least one line of chemotherapy. The primary endpoint is objective response rate, and secondary endpoints include duration of response, progression-free survival, overall survival and safety. The study, which exceeded its expected enrollment of 84 patients with 88 patients enrolled, is being conducted in sites across Asia Pacific, Australia, Europe and North America.

The JAVELIN clinical trial program also includes a Phase III study in Stage IIIb/IV or recurrent non-small cell lung cancer (NSCLC) designed to assess the efficacy and safety of avelumab compared with docetaxel in patients who have experienced disease progression after receiving a prior platinum-containing doublet therapy (JAVELIN Lung 200); a Phase Ib, open-label, multicenter, multiple-dose trial designed to estimate the maximum tolerated dose and select the recommended Phase II dose of avelumab in combination with axitinib** in patients with previously untreated advanced renal cell carcinoma (RCC, JAVELIN Renal 100); an international Phase I open-label, multiple ascending dose trial to investigate the safety, tolerability, pharmacokinetics, biological and clinical activity in patients with metastatic or locally advanced solid tumors (JAVELIN Solid Tumor); and a Phase I trial to investigate the tolerability, safety, pharmacokinetics, biological, and clinical activity of avelumab in Japanese patients with metastatic or locally advanced solid tumors (JAVELIN Solid Tumor Japan) with an expansion part in Asian patients with gastric cancer.

The clinical development program for avelumab now includes more than 1,000 patients treated across more than 15 tumor types, including NSCLC, breast cancer, gastric cancer, ovarian cancer, urothelial cancer (e.g. bladder), esophageal cancer, SCCHN, RCC, MCC, melanoma and mesothelioma.