On January 27, 2016 Incyte Corporation (Nasdaq: INCY) reported that the Phase 2 sub-study of ruxolitinib or placebo in combination with regorafenib in patients with relapsed or refractory metastatic colorectal cancer (CRC) and high C-reactive protein (CRP) will be stopped early (Press release, Incyte, JAN 27, 2016, View Source [SID:1234508874]). The decision to stop the sub-study was made after a planned interim analysis of the high CRP subgroup demonstrated that ruxolitinib plus regorafenib did not show a sufficient level of efficacy to warrant continuation. Schedule your 30 min Free 1stOncology Demo! "We are disappointed at the outcome from this interim analysis and deeply grateful for the support and commitment of the patients participating in the study, their families, and the study investigators," said Steven Stein, M.D., Chief Medical Officer of Incyte.
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About the Study
This Phase 2 randomized, double-blind study (INCB 18424-267) of patients with relapsed or refractory metastatic CRC included an open-label, safety run-in, to confirm the safety of the ruxolitinib plus regorafenib combination in subjects with relapsed or refractory metastatic CRC as well as a randomized phase of the study. The randomized phase of the study included 2 sub-studies targeting separate populations of patients with CRC based on levels of systemic inflammation, as measured by the modified Glasgow Prognostic Score (sub-study 1 CRP >10 mg/L and sub-study 2 CRP ≤ 10 mg/L). Patients in each sub-study were randomized 1:1 to receive ruxolitinib plus regorafenib or regorafenib plus placebo.
About Ruxolitinib (Jakafi)
Ruxolitinib (Jakafi) is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea. Jakafi is also indicated for treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF, and post–essential thrombocythemia MF.
Ruxolitinib is not approved anywhere in the world as treatment for metastatic colorectal cancer.
Full Prescribing Information, including a more complete discussion of the risks associated with Jakafi, is available at www.jakafi.com.
Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States.
Author: [email protected]
Radius Health Announces Clinical Collaboration With a Leading Pharmaceutical Company to Evaluate RAD1901 Combination Regimens in Advanced Breast Cancer
On January 27, 2016 Radius Health, Inc. (Nasdaq:RDUS) reported that it has entered into a worldwide clinical collaboration with Novartis Pharmaceuticals (NYSE:NVS) to evaluate the safety and efficacy of combining investigational agent RAD1901, a novel oral selective estrogen receptor degrader (SERD), with investigational agent LEE011 (ribociclib)*, a cyclin-dependent kinase (CDK) 4/6 inhibitor(Press release, Radius, JAN 27, 2016, View Source [SID:1234508873]). Preclinical studies of RAD1901 have shown consistent and robust single agent anti-tumor activity in multiple wild type and ESR1-mutant breast cancer models and tumor regression when combined with targeted agents such as CDK 4/6 inhibitors in pre-clinical models. The parties also intend to conduct pre-clinical studies to evaluate the effects of RAD1901 in combination with BYL719 (alpelisib), an investigational phosphoinositide 3-kinase (PI3K) inhibitor, with the goal of initiating future clinical trials.
"We are pleased to begin work with Novartis to explore the potential clinical benefits of RAD1901 in combination with these promising investigational agents for breast cancer, the second most common cancer in the world and the most prevalent cancer in women," said Robert Ward, President and Chief Executive Officer of Radius Health. "This collaboration will evaluate the potential of combination therapies to generate improved clinical results, as compared to single agents alone, and to address the needs of these underserved patient populations."
Under the agreement, Radius and Novartis will each contribute resources and supply compound material necessary for the studies to be conducted under the collaboration and will share third party out-of-pocket research and development expenses. The agreement is non-exclusive and each party will solely own all rights to any invention or discovery solely related to its respective product and/or compound. The parties will jointly own all data and inventions related to the combination use of investigational drug RAD1901 with investigational drugs LEE011, BYL719 or another compound arising under the collaboration.
*LEE011 was developed by the Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceutica
Clovis Oncology Initiates Immunotherapy Combination Trial
On January 27, 2016 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that it initiated a clinical trial to evaluate a novel combination therapy of Genentech’s investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PD-L1) and rociletinib for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) (Press release, Clovis Oncology, JAN 27, 2016, View Source [SID:1234508872]). Rociletinib is the Company’s novel, oral targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Schedule your 30 min Free 1stOncology Demo! The Phase 1b/2 trial of rociletinib in combination with atezolizumab, which is sponsored by Clovis, is designed to assess the safety and activity of the combination in patients with activating EGFR mutation-positive (EGFRm) advanced or metastatic NSCLC. The Phase 1b portion of the trial will evaluate the safety, tolerability and pharmacokinetics of the combination in this population. The Phase 2 portion of the trial will evaluate the activity of the combination in two subgroups of patients with EGFR-mutant advanced or metastatic NSCLC: those who have not previously received an EGFR tyrosine kinase inhibitor (TKI) or chemotherapy, and those who have progressed on a prior EGFR TKI. T790M-negative and T790M-positive patients will be enrolled in the Phase 1b portion of the trial and in the Phase 2 portion of the trial in the subgroup of patients who have progressed on a prior EGFR TKI. While patients’ tumors are not required to express PD-L1 to enroll in the study, PD-L1 expression will be assessed in archival and/or fresh tissue as part of the study.
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The University of California in Los Angeles (UCLA) is the first site to initiate the trial, with the first patient expected to be enrolled within a few weeks. Additional patients will begin to enroll in sites throughout the U.S. and E.U., and initial safety and tolerability results from the study are expected at the World Conference on Lung Cancer in the fall of 2016.
"We are pleased to be enrolling patients at UCLA to explore this combination therapy for advanced EGFR-mutant non-small cell lung cancer patients, for whom additional treatment options are needed," said Dr. Jonathan Goldman, Director, Clinical Trials in Thoracic Oncology, Associate Director of Drug Development at UCLA and Principal Investigator. "We obviously hope to see meaningful synergy and patient benefit by combining the effects of immuno-oncology with a targeted therapy."
"I am excited to explore this combination with rociletinib to determine if we can bring the promise of long-term benefit of PD-L1 inhibitors seen in other lung cancer sub-types to those patients with mutant EGFR driven tumors", said Professor Jean-Charles Soria, Professor of Medicine and Medical Oncology at Paris University XI, Cancer Specialist at Gustav Roussy and lead Principal Investigator.
Currently, rociletinib is under review by the U.S. Food and Drug Administration and European Medicines Agency.
"Rociletinib’s activity and safety profile observed in our monotherapy trials suggest that rociletinib may be an attractive agent for combination use," said Patrick Mahaffy, President and CEO of Clovis Oncology. "We are committed to exploring the potential of rociletinib both as monotherapy and in combination to help patients with lung cancer who may benefit."
About Rociletinib
Rociletinib is the company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Data from both the pivotal, single-arm TIGER-X and TIGER-2 clinical trials served as the basis for the U.S. and EU regulatory submissions for the treatment of advanced mutant EGFR T790M-positive lung cancer. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014.
About Lung Cancer and EGFR Mutations
Lung cancer is the most common cancer worldwide with 1.35 million new cases annually, with NSCLC accounting for almost 85 percent of all lung cancers. NSCLC progresses rapidly with a five-year survival rate in advanced NSCLC patients of less than five percent. EGFR activating mutations occur in approximately 10 to 15 percent of NSCLC cases in Caucasian patients and approximately 30 to 35 percent in East Asian patients. These patients often experience significant tumor response to erlotinib, afatinib and gefitinib, which are first- and second-generation EGFR inhibitors. However, most patients ultimately progress on these therapies, with approximately 60 percent of patients developing acquired resistance from a second, "gatekeeper" mutation, T790M.
ImmunoCellular Therapeutics Enters into a Sponsored Research Agreement with The University of Maryland, Baltimore to Pursue Multiple Enhancements of its Cancer Immunotherapy Platforms
On January 27, 2016 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported it has entered into a sponsored research agreement with Eduardo Davila, PhD, Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine, and the University of Maryland, Baltimore (Press release, ImmunoCellular Therapeutics, JAN 27, 2016, View Source [SID:1234508866]). The agreement includes three projects, which together have the potential to improve the efficacy of dendritic cell, T-cell, and combination immunotherapies for cancer and lead to enhancements to both of ImmunoCellular’s dendritic cell and Stem-to-T-cell platforms. Schedule your 30 min Free 1stOncology Demo! The first of three projects evaluates certain immune modulators that could enhance T-cell killing of tumor cells. These small molecule modulators have been shown preclinically to be capable of increasing tumor antigen expression while simultaneously decreasing expression of ligands, such as PD-L1 and PDL2, which decrease T-cell activity. This technology applies directly to both ImmunoCellular platforms.
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The second project explores the combination of engineered killer T-cells and dendritic cell immunotherapies on tumor killing. These T-cells embody a novel engineering technology that potentially amplifies their cytotoxic, proliferative, and cytokine-producing properties toward tumor antigens. Combining these engineered T-cells with ImmunoCellular’s dendritic cell immunotherapies could lead to enhanced tumor cell killing.
The third project tests novel peptide configurations for use with dendritic cell immunotherapies to potentially induce enhanced T-cell responses.
Dr. Davila is the Program Leader for the Tumor Immunology and Immunotherapy Program within the University of Maryland Marlene and Stewart Greenebaum Cancer Center Program. As such, he collaborates with both basic and clinical research investigators to understand the immune regulation of malignant disease and translate this knowledge into the development of novel diagnostic, preventative and treatment regimens.
"ImmunoCellular’s research and early development strategy is to complement and enhance our dendritic cell and Stem-to-T-cell technology platforms and create potent cell-based cancer immunotherapeutic clinical candidates and combinations," said Steven Swanson, PhD, ImmunoCellular Senior Vice President, Research. "The research projects we are undertaking with Dr. Davila align well with this strategy and have the potential to lead to platform technology enhancements and new clinical programs."
"With this agreement and with other related research underway, we are systematically delivering on our goal to build a leading cancer immunotherapy company. We are pleased with the enhanced position we are establishing in the dendritic cell and T-cell cancer immunotherapy space," said Andrew Gengos, ImmunoCellular Chief Executive Officer.
INIVATA COMPLETES £31.5 MILLION ($45M) SERIES A FUNDRAISING ROUND
On January 26, 2016 Inivata Limited, a clinical cancer genomics company employing the precision of circulating tumour DNA ("ctDNA") analysis to improve personalized healthcare in oncology, reported the completion of a Series A fundraising of £31.5 Million ($45M) (Press release, Cancer Research Technology, JAN 26, 2016, View Source [SID1234523507]). Existing investors Imperial Innovations, Cambridge Innovation Capital, and Johnson & Johnson Innovation – JJDC, Inc. all participated in the round, as did new investor Woodford Patient Capital Trust.
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"Since Inivata’s seed funding sixteen months ago, the market has seen an explosion of interest and funding in liquid biopsy research. With our early presence in Cambridge, UK and our imminent presence in the USA, we are well-placed to be forerunners in the practical application of liquid biopsy for clinical oncologists," said Michael Stocum, Chief Executive Officer of Inivata. "We are grateful to our existing investors for their continued strong support of Inivata and very pleased to welcome Woodford Patient Capital Trust to augment what is already a very strong investor base. Our mission is to partner with oncologists to revolutionize cancer treatments and outcomes for their patients – part of a new landscape of personalized healthcare."
The new funds will be used to accelerate clinical studies to validate Inivata’s technology platform based on enhanced TAm-Seq, and commercialize the company’s first products. Inivata’s platform will initially be applied across a spectrum of solid tumors, including lung, breast and colon cancer to demonstrate the integration of genomic information with clinically actionable decision-making, thereby defining a personalized approach to cancer care.
"Inivata has advanced significantly since inception and is poised to become a leader in the rapidly-growing field of ctDNA analysis," said Rob Woodman, Director of Healthcare Investments at Imperial Innovations. "This fundraising reflects the great progress the company has made in developing innovative molecular profiling and monitoring products that will have real impact on patient care, and will help strengthen the platform for the company to roll these products out."
Inivata’s proprietary technology represents a new generation of non-invasive molecular profiling from a simple blood draw that is poised to impact the major aspects of a patient’s care including diagnosis, prognosis, treatment stratification and response monitoring. The test, which allows precise analysis of cancer-related mutations present in ctDNA, is designed to provide oncologists with clinically actionable genomic information to guide therapy selection, monitor treatment progress and, importantly, detect new mutations as they emerge. The genomic analysis of ctDNA has the potential to transform cancer care and resolve many of the limitations inherent in current tissue-based testing protocols that are highly invasive and are not amenable to serial monitoring in routine practice. Inivata’s platform is based on pioneering research from the Rosenfeld Lab at the Cancer Research UK Cambridge Institute (CRUK-CI) and to date, Inivata has demonstrated putative clinical utility of enhanced TAm-Seq through published clinical work presented at multiple cancer conferences in the fall of 2015.
"We have been impressed with the results thus far from Inivata’s initial clinical studies that highlight the sensitivity and accuracy of the Company’s ctDNA platform. Inivata is already working with a strong network of clinicians in both Europe and the United States and this new funding will allow the company to accelerate its clinical validation and commercialization efforts," said Robert Tansley of Cambridge Innovation Capital.