On May 19, 2016 AstraZeneca and its global biologics research and development arm, MedImmune, reported that they will provide an update on their extensive oncology pipeline at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, USA, on 3-7 June 2016 (Press release, AstraZeneca, MAY 19, 2016, View Source [SID:1234512562]).

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Highlights will include new data demonstrating the strength and versatility of AstraZeneca’s industry-leading line of DNA damage response (DDR) medicines in multiple types of cancer. New data will highlight the continued momentum behind AstraZeneca’s numerous immuno-oncology (IO) programmes, and showcase small-molecule developments including Tagrisso (osimertinib) in leptomeningeal (brain) disease and the highly-selective Bruton’s tyrosine kinase (BTK) inhibitor, acalabrutinib, in chronic lymphocytic leukaemia (CLL).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Oncology is a strategic priority for AstraZeneca because of the potential of our broad pipeline to offer transformational therapies in cancer care. At ASCO (Free ASCO Whitepaper), we will update on our next-generation portfolio focusing on DNA damage response as a breakthrough paradigm in cancer treatment, including new long-term overall survival data for Lynparza. Our increased commitment to DDR therapies complements developments in our exciting immuno-oncology pipeline, from which we are expecting clinical results over the coming year."

DDR: A promising scientific platform, a leading position for AstraZeneca

DDR is a term describing the network of cellular pathways that minimise the daily impact of DNA damage. Currently, many cancers are known to have defects in DDR pathways, which makes them dependent on and therefore, highly sensitive to inhibition of the remaining DDR pathways. Targeting DDR deficiencies to preferentially kill cancer cells, while minimising the impact on normal cells, has potential for more selective, better tolerated therapies to improve survival in multiple cancers.

AstraZeneca is developing a comprehensive pipeline of compounds that target molecular pathways across the DDR system. These include the PARP inhibitor Lynparza (olaparib); Wee1 inhibitor AZD1775, ATM inhibitor AZD0156; ATR inhibitor AZD6738, and Aurora B Kinase inhibitor AZD2811. These compounds act on different cell-cycle points to prevent tumour cells from reproducing.

At the ASCO (Free ASCO Whitepaper) congress, DDR presentations will highlight:

The potential for maintenance of DDR therapies as shown by Lynparza overall survival data from Study 19 in ovarian cancer (Abstract # 5501). This abstract has been selected as a "Best of ASCO (Free ASCO Whitepaper)" abstract.
Opportunities for combination approaches with DDR and immuno-oncology therapies as shown in a Phase I study of the PD-L1 inhibitor, durvalumab, in combination with Lynparza or a VEGFR inhibitor, cediranib, in women’s cancers (Abstract # 3015)
The importance of selecting patients with a DDR pathway defect using the right diagnostic tool (abstract #4041)
The potential of DDR therapies against multiple biological DDR targets in different tumour types, with studies of the highly-selective WEE1 inhibitor, AZD1775, in advanced high-grade serous ovarian cancer (Abstract # TPS5610), squamous cell carcinoma of the head and neck (SCCHN) (Abstract # TPS6106), advanced solid tumours (Abstract # TPS2608) and glioblastoma (GBM) (Abstract # 2008)
Immuno-Oncology: Robust development momentum on track for read-outs in H1 2017

AstraZeneca is leading in a number of first-line studies with its IO strategy, where combined PD-L1 and CTLA-4 blockade – through the combination of durvalumab and tremelimumab – may address a significant unmet medical need for cancer patients who may not benefit from PD-1 pathway drugs in monotherapy.

Key updates include presentations covering pre-clinical data, late-stage trials and biomarker research:

Early study results of durvalumab monotherapy in urothelial bladder cancer from Phase Ib Study 1108 (Abstract # 4502)
Final results from a Phase III study of tremelimumab in mesothelioma (Abstract # 8502)
New study results on safety and clinical activity of durvalumab as first-line treatment in non-small cell lung cancer (NSCLC) (Abstract # 9029)
Ongoing investigation of the potential synergistic effects of durvalumab and the CTLA-4 inhibitor, tremelimumab, in bladder cancer (DANUBE trial – Abstract # TPS4574) and SCCHN (KESTREL trial – Abstract # TPS6101)
Enhanced understanding of PD-L1 biomarker expression in relation to primary versus metastatic tumours and sample age (Abstract # 3025)
Tagrisso in brain metastasis; acalabrutinib in CLL

AstraZeneca’s strong heritage in developing innovative targeted small molecules was underscored by the recent approval of Tagrisso as the first indicated treatment for EGFR T790M mutation-positive metastatic NSCLC in the US, EU and Japan. At ASCO (Free ASCO Whitepaper), new data will highlight the importance of Tagrisso activity in leptomeningeal disease through its ability to penetrate the blood-brain barrier. Further presentations will show the growing role of circulating tumour DNA (ctDNA) testing for diagnosis and treatment monitoring.

Key updates will also include presentation on the potential of our potent, highly-selective BTK inhibitor, acalabrutinib, in chronic lymphocytic leukaemia (CLL):

Data from the BLOOM study of Tagrisso in patients with leptomeningeal disease as a complication of EGFRm-metastatic NSCLC (Abstract # 9002)
Intensive plasma ctDNA profiling in experimental trials to identify markers of acquired drug resistance (Abstract # 11530)
Acalabrutinib – preliminary results from a first-line study as first-line therapy in CLL (Abstract # 7521) and in a Phase II study in combination with pembrolizumab in metastatic pancreatic cancer (Abstract # 4130)

May 19, 2016 Varian Medical Systems (NYSE: VAR) reported that it has been selected by the Apollo Hospitals Group to supply 12 advanced medical linear accelerators and five brachytherapy systems as India’s largest private hospital chain rolls out a program to replace ageing cancer treatment machines (Press release, InfiMed, MAY 19, 2016, View Source [SID:1234512584]). Based on an order placed in March, Varian will supply 11 TrueBeam systems, one Edge Radiosurgery system, and five GammaMed brachytherapy systems for the Apollo network over the next two years.

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The Edge Radiosurgery system, which will be installed in one of Apollo’s tertiary care centers, is a precise, non-invasive alternative to conventional surgery. With enhanced precision and speed, the Edge system offers state of the art radiosurgery and can treat a wide range of conditions across an ever increasing number of clinical indications. Varian’s flagship TrueBeam family of linear accelerators, to be installed at hospitals throughout the Apollo chain, incorporates numerous technical innovations that dynamically synchronize imaging, patient positioning, motion management, and treatment delivery during a radiotherapy or radiosurgery procedure.

As well as advanced treatment equipment, Apollo is ordering a full suite of Varian software tools including the Eclipse treatment planning system and ARIA oncology information management system, along with specific modules such as RapidPlan to enhance the speed and quality of treatment plans, and the InSightive Analytics real-time dashboard to maximize workflow in a clinic.

"We are pleased that Apollo has selected our technology-leading hardware and software to offer their cancer patients fast and precise treatments," says Ashok Kakkar, senior managing director of Varian India. "India is severely under-equipped when it comes to radiotherapy treatment machines and more than two million new cancer cases are detected each year in the country. Programs such as this help to make a big difference in the treatment of cancer patients in India."

Commenting on the collaboration, Dr. Preetha Reddy, executive vice chairperson of Apollo Hospitals Enterprise Limited said, "Healthcare has evolved by leaps and bounds in the past few years and technology has played a critical role in improving clinical outcomes for patients. Providing high quality healthcare on a par with global standards is our prime objective and we are glad to partner with Varian in this endeavor. Already enriched with highly skilled doctors, technicians and physicians, cutting edge technology will further enhance India’s positioning as a global healthcare destination."

Last year, Varian and Apollo announced a collaboration on the first radiotherapy educational co-operation of its kind between industry and a care provider in India. In this collaboration, Varian and Apollo will work together to bring greater access to training in modern radiotherapy by leveraging the existing Apollo Knowledge network that comprises several educational entities in the healthcare space in India. This collaboration with Apollo is a furtherance of Varian’s Access to Care program, which seeks to bridge the gap between the growing need for modern radiotherapy treatment machines in developing countries and the lack of trained personnel to operate them.

On May 19, 2016 GlycoMimetics, Inc. (NASDAQ: GLYC) reported that initial efficacy data from a Phase 1/2 clinical trial on the effects of drug candidate GMI-1271 combined with chemotherapy on patients with acute myeloid leukemia (AML) were accepted as a poster to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper)’s 21st Congress, taking place June 9-12 in Copenhagen, Denmark (Press release, GlycoMimetics, MAY 19, 2016, View Source [SID:1234512607]).

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The poster (P191), entitled "Results of a Phase 1 study of GMI-1271, a novel E-selectin antagonist in combination with induction chemotherapy in relapse/refractory AML: a novel, well-tolerated regimen with a high remission rate," is scheduled for 5:15 p.m. CET on Friday, June 10.

The abstract is available here

About GMI-1271

GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with acute myeloid leukemia (AML) cells in ways that help the cancer cells evade the effects of chemotherapy treatment. Preclinical research points to the drug’s potential role in moving cancerous cells out of the protective environment of the bone marrow where they hide and escape the effects of chemotherapy. By blocking E-selectin, GMI-1271 also may protect normal blood-producing cells, and reduce the toxic side effects of chemotherapy such as low white blood cell counts that make some patients more prone to infections. GMI-1271 may also reduce mucositis (inflammation or lesions in the intestinal tract and mouth), which can be a side effect of chemotherapy. GlycoMimetics has announced encouraging initial top line data from the first two cohorts in its ongoing Phase 1/2 clinical study.

On May 19, 2016 Incyte Corporation (Nasdaq: INCY) reported that more than 20 abstracts featuring its clinical development candidates will be presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and European Hematology Association (EHA) (Free EHA Whitepaper) annual meetings (Press release, Incyte, MAY 19, 2016, View Source;p=RssLanding&cat=news&id=2169771 [SID:1234512564]). These conferences will take place from June 3–7, 2016 (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois and June 9–12, 2016 (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark.

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"The abstracts to be presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) illustrate both the diversity and the potential of our rich portfolio," stated Steven Stein, M.D., Incyte’s Chief Medical Officer. "We are especially pleased to present long-term data from the COMFORT-I Phase 3 study, which further advances the understanding of Jakafi in the treatment of patients with myelofibrosis. These five-year data, along with additional new data from capmatinib, our potent and highly selective c-MET inhibitor licensed to Novartis, underscore Incyte’s commitment to researching and progressing innovative therapies that have the potential to transform the lives of patients living with cancer."

Select ASCO (Free ASCO Whitepaper) Abstracts

Myelofibrosis
Long-term Outcomes of Ruxolitinib Therapy in Patients with Myelofibrosis: 5-Year Update from COMFORT-I (Abstract #7012)
June 6, 2016, 8:00–11:30 a.m., E354b Hall A
ReTHINK: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of Ruxolitinib in Early Myelofibrosis patients with High Molecular Risk Mutations (Abstract #TPS7080)
June 6, 2016, 8:00–11:30 a.m., Hall A, Poster Board #67b

Solid Tumors
GEOMETRY duo-1: A Phase Ib/II, Multicenter Trial of Oral cMET inhibitor Capmatinib (INC280) ± Erlotinib vs. Platinum/Pemetrexed in Adult Patients with Epidermal Growth Factor Receptor (EGFR)-mutated, cMET-amplified, Locally Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC) with Acquired Resistance to Prior EGFR Tyrosine Kinase Inhibitor (TKI) Therapy (Abstract #TPS9109)
June 4, 8:00–11:30 a.m., Hall A, Poster Board #427a
Phase I Study of the Safety and Efficacy of the c-MET Inhibitor Capmatinib (INC280) in Patients with Advanced c-MET+ NSCLC (Abstract #9067)
June 4, 8:00–11:30 a.m., Hall A, Poster Board #390
Phase II Study of the Efficacy and Safety of the c-MET Inhibitor Capmatinib (INC280) in Patients with Advanced Hepatocellular Carcinoma (Abstract #4074)
June 4, 8:00–11:30 a.m., Hall A, Poster Board #66
Phase II Safety and Efficacy Results of a Single-arm Phase Ib/II Study of Capmatinib (INC280) + Gefitinib in Patients with EGFR-mutated, c-MET-positive Non-small Cell Lung Cancer (NSCLC) (Abstract #9020)
June 4, 3:00–4:15 p.m., E354b Hall A
Select EHA (Free EHA Whitepaper) Abstracts
Myelofibrosis
Long-Term Outcomes of Ruxolitinib Therapy in Patients with Myelofibrosis: 5-Year Final Efficacy and Safety Analysis from COMFORT-I (Abstract #S452)
June 11, 11:30–11:45 a.m., Hall A3
Safety and Efficacy of Ruxolitinib in Patients with Dipss Intermediate-1–Risk Myelofibrosis from JUMP: An Open-Label, Multicenter, Single-Arm Expanded-Access Study (Abstract # P296)
June 10, 5:15–6:45 p.m., Hall H
Polycythemia Vera
Ruxolitinib Reduces JAK2V617F Allele Burden in Patients with Polycythemia Vera enrolled in the RESPONSE Study (Abstract #S454)
June 11, 12:00–12:15 p.m., Hall A3
Ruxolitinib Proves Superior to Best Available Therapy in Patients with Polycythemia Vera Resistant to or Intolerant of Hydroxyurea and a Nonpalpable Spleen; Results from RESPONSE-2 (Abstract #S112)
June 10, 12:00–12:15 p.m., Auditorium 1
Essential Thrombocythaemia
Ruxolitinib Compared with Best Available Therapy for Essential Thrombocythaemia Patients Resistant or Intolerant to Hydroxycarbamide in MAJIC – An Investigator Lead Randomized Trial (Abstract #LB304)
June 10, 5:15–6:45 p.m., Hall H
Full session details and data presentations at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting can be found at: View Source Full session details and data presentations at the 21st Congress of the EHA (Free EHA Whitepaper) can be found at: http://www.ehaweb.org/congress-and-events/21st-congress/program/program-by-day/.
About Jakafi (ruxolitinib)
Ruxolitinib is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration, as Jakafi (ruxolitinib), 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.
Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States.
Important Safety Information
Jakafi can cause serious side effects, including:
Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.
Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.
Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.
Increases in Cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.
The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache.
These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.
Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider. Do not drink grapefruit juice while on Jakafi.
Women should not take Jakafi while pregnant or planning to become pregnant, or if breast-feeding.
Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at www.jakafi.com.

On May 19, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that new data will be presented for duvelisib, an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place from June 9 – 12, 2016, in Copenhagen (Press release, Infinity Pharmaceuticals, MAY 19, 2016, View Source;p=RssLanding&cat=news&id=2169736 [SID:1234512585]). At the meeting, preliminary data from CONTEMPO, a Phase 1b/2 study evaluating duvelisib in combination with rituximab or obinutuzmab in treatment-naïve follicular lymphoma patients, will be presented in a poster session. Duvelisib is the only dual inhibitor of PI3K-delta,gamma in Phase 3 clinical development and is in registration-focused studies in patients with relapsed/refractory indolent non-Hodgkin lymphoma (iNHL) and relapsed/refractory chronic lymphocytic leukemia (CLL). Infinity and AbbVie are jointly developing duvelisib in oncology.

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Additionally, posters reviewing ongoing clinical studies of duvelisib and IPI-549, Infinity’s investigational immuno-oncology development candidate that selectively inhibits PI3K-gamma, will be presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago from June 3 – 7, 2016.

Presentations and publications are listed below. All abstracts are available on the conference websites.

EHA 2016
Friday, June 10, 2016, 11:15 a.m. ET – 12:45 p.m. ET (5:15 p.m. – 6:45 p.m. CEST) (poster presentation)
Title: Preliminary Safety, Pharmacokinetics, and Pharmacodynamics of Duvelisib Plus Rituximab or Obinutuzumab in Patients with Previously Untreated CD20+ Follicular Lymphoma
Abstract Number: P319
Lead Author: Carla Casulo, M.D., James P. Wilmont Cancer Center Strong Memorial Hospital, University of Rochester
Location: Hall H

ASCO 2016
Sunday, June 5, 2016, 9:00 a.m. – 12:30 p.m. ET (8:00 a.m. – 11:30 a.m. CT) (poster session)
Title: IPI-549-01-A phase 1/1b First-in-Human Study of IPI-549, a PI3K-Gamma Inhibitor, as Monotherapy and in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
Abstract Number: TPS3111
Lead Author: Anthony W. Tolcher, M.D, Director of Clinical Research, South Texas Accelerated Research Therapeutics (START)
Location: Hall A

Monday, June 6, 2016, 9:00 a.m. – 12:30 p.m. ET (8:00 a.m. – 11:30 a.m. CT) (poster session)
Title: FRESCO: A Phase 2, Randomized Study of Duvelisib Plus Rituximab vs R-CHOP in Patients with Relapsed/Refractory Follicular Lymphoma Who Have Progressed within 24 Months of Receiving an Alkylator-Based Chemotherapy Regimen.
Abstract Number: TPS7578
Lead Author: Nathan Fowler, M.D., Associate Professor at the Department of Lymphoma/Myeloma, University of Texas, MD Anderson Cancer Center
Location: Hall A

ASCO Publication Only
Title: Preliminary Safety, Pharmacokinetics, and Pharmacodynamics of Duvelisib Plus Rituximab or Obinutuzumab in Patients with Previously Untreated CD20+ Follicular Lymphoma
Abstract Number: #e19052
Lead Author: Carla Casulo, M.D., James P. Wilmont Cancer Center Strong Memorial Hospital, University of Rochester

About Duvelisib
Duvelisib is an investigational dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, two proteins that are known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment. 1-3AbbVie and Infinity Pharmaceuticals, Inc. are jointly researching and developing duvelisib in various cancer types.

Duvelisib is being evaluated in several studies, including a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma4, a Phase 3 study in combination with other agents in patients with previously treated follicular lymphoma5 and a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia6. Duvelisib is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

These are investigational drugs being studied for indications that have not been approved by Regulatory Agencies. Safety and efficacy have not been established in unapproved indications.