On December 9, 2015 Genmab A/S (Nasdaq Copenhagen: GEN) reported it has reached a USD 5 million milestone in its daratumumab collaboration with Janssen Biotech, Inc. (Janssen) (Press release, Genmab, DEC 9, 2015, View Source [SID:1234508516]).

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 milestone payment was triggered by progress in the ongoing Phase II study ("Carina" LYM2001) of daratumumab in NHL. The study evaluates daratumumab monotherapy in three different types of NHL, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL). This milestone is related to progress in the arm of the study treating patients with DLBCL.

"Daratumumab is being investigated in numerous studies for multiple myeloma, covering all lines of therapy. We are very pleased to report progress in the first study of daratumumab in an indication beyond multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Daratumumab has received Orphan Drug designation from the US FDA for DLBCL, MCL and FL.
Today’s news does not impact Genmab’s 2015 financial guidance.

About the LYM2001 study
This Phase II study (NCT02413489) is a three arm (DLBCL, FL, MCL), open-label multicenter study which will enroll up to 210 patients with relapsed or refractory non-Hodgkin’s lymphoma. Patients in the study will be treated with daratumumab monotherapy. The primary endpoint of the study is overall response rate. The safety profile of daratumumab in these diseases will also be assessed.

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.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. 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,1,2 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,1,2 antibody-dependent cellular phagocytosis3,4 and antibody-dependent cellular cytotoxicity.1,2 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and a subset of regulatory T cells (Tregs) both of which express CD38. These reductions in MDSCs and Tregs were paralleled by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.1

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 and non-Hodgkin’s lymphoma.

On December 9, 2015 Merck and Pfizer reported the initiation of two Phase III studies of avelumab*, an investigational, fully human anti-PD-L1 IgG1 monoclonal antibody, in treating advanced or metastatic gastric/gastro-esophageal junction (GEJ) cancers, which are aggressive cancers with poor survival rates (Press release, Merck KGaA, DEC 9, 2015, View Sourcepfizer.com/news/press-release/press-release-detail/merck_kgaa_darmstadt_germany_and_pfizer_initiate_two_phase_iii_studies_of_investigational_immunotherapy_avelumab_in_advanced_gastric_and_gastro_esophageal_junction_cancers" target="_blank" title="View Sourcepfizer.com/news/press-release/press-release-detail/merck_kgaa_darmstadt_germany_and_pfizer_initiate_two_phase_iii_studies_of_investigational_immunotherapy_avelumab_in_advanced_gastric_and_gastro_esophageal_junction_cancers" rel="nofollow">View Source [SID:1234508513]).

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!

These pivotal trials are investigating avelumab in the first-line and third-line settings, with overall survival (OS) as the primary endpoint in both trials.

JAVELIN Gastric 100, a study comparing the switch from first-line chemotherapy to maintenance therapy with avelumab versus continuation of chemotherapy, is a multicenter, international, randomized, open-label Phase III trial designed to evaluate the potential superiority (based on OS) of maintenance therapy with avelumab in patients with unresectable, locally advanced or metastatic gastric/GEJ cancers whose disease has not progressed with first-line platinum-based chemotherapy. This is currently the only Phase III trial in gastric cancer that is designed to evaluate superiority of an immunotherapy compared with conventional platinum-based chemotherapy as a first-line maintenance treatment. The study will enroll 629 patients across more than 220 sites in Asia Pacific, Europe, North America and South America.

"The prognosis is generally poor for the majority of patients with advanced gastric cancers," said Dr. Luciano Rossetti, Head of Global Research & Development at Merck’s biopharma business. "By initiating these two Phase III trials in gastric and gastro-esophageal junction cancers, we are continuing the fight against cancer with an overarching goal of potentially improving survival for patients."

The third-line study, JAVELIN Gastric 300, is a multicenter, international, randomized, open-label Phase III trial designed to evaluate the potential superiority (based on OS) of avelumab in patients with unresectable, recurrent or metastatic gastric/GEJ cancers, compared with investigator’s choice of chemotherapy from a pre-specified list of therapeutic options. The study will enroll approximately 330 patients, spanning approximately 170 sites in Asia, Australia, Europe, North America and South America.

"We are continuing to investigate avelumab in cancers with high unmet need and where there is a strong rationale for immunotherapeutic intervention," said Dr. Mace Rothenberg, Senior Vice President of Clinical Development and Medical Affairs and Chief Medical Officer for Pfizer Oncology. "Advanced gastric cancer is a challenging diagnosis to face as a patient, and we are dedicating significant resources to evaluate avelumab as a potential new treatment option for patients in multiple settings of this disease."

The clinical development program for avelumab now includes more than 1,500 patients who have been treated across more than 15 tumor types, including breast cancer, gastric/GEJ cancers, head and neck cancer, Merkel cell carcinoma, melanoma, mesothelioma, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and urothelial (e.g. bladder) cancer. Clinical trials for both of the gastric/GEJ Phase III trials in North America will be conducted on behalf of Merck by EMD Serono, the company’s US and Canadian biopharma business.

*Avelumab is the proposed International Non-proprietary Name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

References
1. Waddell T et al. Ann Oncol 2013;24 Suppl 6:vi57-63.
2. Wadhwa R et al. Nat Rev Clin Oncol 2013;10(11):643-55.
3. American Cancer Society. Survival rates for stomach cancer, by stage. Available from: View Sourcecancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-survival-rates." target="_blank" title="View Sourcecancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-survival-rates." rel="nofollow">View Source Last accessed December 2015.
4. National Cancer Institute Surveillance Epidemiology and End Results (SEER). SEER Stat Fact Sheets: Stomach Cancer. Available from: View Source stomach.html. Last accessed April 2015.
5. International Agency for Research on Cancer (IARC)/EUCAN. Gastric cancer: Estimated incidence, mortality & prevalence for both sexes, 2012. Available from: http:// eco.iarc.fr/EUCAN/Cancer.aspx?Cancer=8#block-table-a. Last accessed April 2015.
6. Mayo Clinic. Stomach cancer treatments and drugs. Available from: View Source mayoclinic.org/diseases-conditions/stomach-cancer/basics/treatment/con-20038197. Last accessed April 2015.
7. Buas MF & Vaughan TL. Semin Radiat Oncol. 2013; 23(1): 3-9.
8. Cunningham D et al. New Eng J Med 2006;355(1):11-22.
9. Macdonald JS et al. N Eng J Med 2001;345(10):725-30.
10. Cancer Research UK. What is advanced oesophageal junction cancer? View Source cancerresearchuk.org/about-cancer/type/oesophageal-cancer/treatment/advanced/what-is-advanced-oesophageal-cancer. Last accessed September 2015.

About Gastric and Gastro-esophageal Junction (GEJ) Cancers
Gastric cancer is uncommon in the US and Western Europe.1,2 Each year, there are approximately 22,000 new cases of gastric cancer diagnosed in the US and 80,626 cases diagnosed in the EU.3 Gastric cancer is much more commonly diagnosed in East Asia, Eastern Europe, and parts of South America.4 For patients with advanced gastric cancer, the prognosis is poor. The 5-year survival rate in the US is <20 percent for Stage III gastric cancer and <5 percent for Stage IV gastric cancer.5 Current treatment options for gastric cancer may include surgery, radiotherapy, chemotherapy, chemoradiotherapy and targeted therapies.2,6
Reliable data on the global incidence of GEJ tumors are not available, due to the historically complicated classification system and the likelihood of misclassification.7 Current treatment options for GEJ cancer may include surgery, chemotherapy, radiation therapy and targeted therapy.8,9 Despite advances in the field of GEJ, there is no cure for patients with cancer that has spread.10 There is a clear unmet medical need for new treatment options.

About Avelumab
Avelumab (also known as MSB0010718C) is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

On December 9, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported the initiation of STARTRK-NG, a new pediatric Phase 1/1b clinical trial of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors that harbor activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK (Press release, Ignyta, DEC 9, 2015, View Source [SID:1234508511]).

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!

STARTRK-NG (which stands for "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases – Next Generation") is a multicenter, open label, dose-escalation and expansion study designed to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), tolerability, pharmacokinetics and preliminary clinical activity of entrectinib in children and adolescents with recurrent or refractory extracranial solid tumors or primary central nervous system (CNS) tumors, including indications such as neuroblastoma.

"We are excited to expand the clinical development program for entrectinib with this first clinical study in pediatric patients," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "There is abundant scientific evidence suggesting that inhibition of oncodrivers such as Trk and ALK could be effective in many cancers in children and adolescents. Because entrectinib is the most potent Trk inhibitor in the clinic, without undesirable off-target activity, as well as a potent inhibitor of ALK, and given entrectinib’s clinically demonstrated activity in the central nervous system, we look forward to conducting this study of entrectinib for the benefit of these patients."

The clinical sites participating in the STARTRK-NG trial are the four Alex’s Lemonade Stand Foundation for Childhood Cancer Centers of Excellence:

The Children’s Hospital of Philadelphia,
Dana-Farber/Boston Children’s Cancer Hospital,
Texas Children’s Cancer Center, and
University of California, San Francisco.

About Entrectinib

Entrectinib is a novel, orally available, selective tyrosine kinase inhibitor targeting tumors that harbor activating alterations to NTRK1/2/3 (encoding TrkA/ TrkB/TrkC), ROS1 or ALK. Entrectinib is the most potent Trk inhibitor in the clinic, without undesirable off-target activity, and the only Trk inhibitor with clinically demonstrated activity against CNS metastases. In addition to the STARTRK-NG trial, this product candidate is in a Phase 2 clinical trial called STARTRK-2. The trial is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types and molecular targets.