On March 31, 2017 Amgen (NASDAQ:AMGN) reported that new preclinical data from its oncology portfolio will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 1-5, 2017, in Washington, D.C (Press release, Amgen, MAR 31, 2017, View Source [SID1234518347]). These data provide insights into the potential of Amgen’s half-life optimized bispecific T cell engager (BiTE) immunotherapy platform across different cancers, as well as the local and systemic immune effects from combining Amgen’s oncolytic virus with a CTLA-4 inhibitor.

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Preclinical data from Amgen’s latest oncology candidate to enter clinical trials (AMG 176) will also be presented. AMG 176 is a potent, highly selective and reversible Mcl-1 inhibitor. A variety of studies have demonstrated that hematologic malignancies, such as multiple myeloma, acute myeloid leukemia and non-Hodgkin lymphoma, are particularly sensitive to Mcl-1 inhibition.

"AACR has always been an important meeting for sharing some of our latest advances in cancer research and 2017 is no exception. This year’s data underscores our commitment to Amgen’s evolving oncology portfolio and to the discovery and development of innovative new therapies," said David Reese, M.D., senior vice president of Discovery Research (interim) and Translational Sciences at Amgen. "In addition to sharing new data for some of our more advanced compounds, we also look forward to sharing research around our first-in-class Mcl-1 inhibitor, a small molecule being investigated for its potential use in patients with hematologic malignancies for which there continues to be a need for new treatment options."

Abstracts are available and can be viewed on the AACR (Free AACR Whitepaper) website at View Source Identified below are selected abstracts of interest on Amgen research.

Mcl-1 Inhibition:

The discovery and preclinical characterization of AMG 176: A first-in-class Mcl-1 inhibitor in clinical development for multiple myeloma
Abstract #DDT01-01, Oral Presentation, Sunday, April 2 from 1–1:24 p.m. ET at Walter E. Washington Convention Center, East Salon A-B, Level 1
Combined targeting of MEK and MCL-1 induces apoptosis and tumor regression of KRAS mutant NSCLC
Abstract #2163, Poster Session, Monday, April 3 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 7
Preclinical evaluation of AMG 176, a novel, potent and selective Mcl-1 inhibitor with robust anti-tumor activity in Mcl-1 dependent cancer models
Abstract #2027, Poster Session, Monday, April 3 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 1
BiTE Antibody Construct:

Generation of half-life extended anti-CD33 BiTE antibody constructs compatible with once-weekly dosing
Abstract #55, Poster Session, Sunday, April 2 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 3
Preclinical evaluation of a BiTE antibody construct with extended half-life that targets the tumor differentiation marker mesothelin
Abstract #3630, Poster Session, Tuesday, April 4 from 8 a.m. – noon ET at Walter E. Washington Convention Center, Halls A-C, Section 26
BiTE antibody constructs for the treatment of SCLC
Abstract #3632, Poster Session, Tuesday, April 4 from 8 a.m. – noon ET at Walter E. Washington Convention Center, Halls A-C, Section 26
Immuno-Oncology:

OncoVEXmGM-CSF (HSV-1 modified similarly to talimogene laherparepvec) icombination with CTLA-4 blockade leads to both local and systemic efficacy in a murine syngeneic model of metastatic melanoma
Abstract #4566, Poster Session, Tuesday, April 4 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 25
Growth Inhibitory Pathway:

Selective MET kinase inhibition in MET-dependent glioma models
Abstract #2077, Poster Session, Monday, April 3 from 1–5 p.m. ET at Walter E. Washington Convention Center, Halls A-C, Section 4
About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

On March 31, 2017 AstraZeneca reported that the US Food and Drug Administration (FDA) has granted full approval for Tagrisso (osimertinib) 80mg once-daily tablets, for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after an EGFR tyrosine kinase inhibitor (TKI) therapy (Press release, AstraZeneca, MAR 31, 2017, View Source [SID1234518328]). Tagrisso is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation, and efficacy data suggest it may be a new standard of care for these patients.

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "By following the science, we aim to turn lung cancer into a chronic, manageable disease for patients and this milestone brings us one step closer to that ambition. The FDA’s full approval reinforces the potential of Tagrisso to become the standard of care for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer whose disease has progressed on or after first-generation EGFR-TKI therapy."

The full approval in the US is based on data from the randomised, Phase III AURA3 trial, in which Tagrisso significantly improved progression-free survival (PFS) versus platinum-based doublet chemotherapy, providing 10.1 months of median PFS compared to 4.4 months from chemotherapy (hazard ratio 0.30; 70% risk reduction; 95% Confidence Interval [CI]: 0.23; 0.41; P<0.001). The results of this trial were recently presented at the 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria, and published in The New England Journal of Medicine.

In AURA3 the most common (>20%) adverse reactions observed in Tagrisso-treated patients were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%). Dose reductions occurred in 2.9% of patients treated with Tagrisso. The most frequent adverse reactions that led to dose reductions or interruptions were prolongation of the QT interval as assessed by ECG (1.8%), neutropenia (1.1%), and diarrhea (1.1%). Serious adverse reactions were reported in 18% of patients treated with Tagrisso and 26% of patients in the chemotherapy group. No single serious adverse reaction was reported in 2% or more patients treated with Tagrisso.

Tagrisso was granted Fast Track, Breakthrough Therapy and Priority Review designations by the US FDA, and received Accelerated Approval for this indication in 2015 based on tumour response rate and duration of response.

About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined. Among patients with NSCLC, 20% to 40% have brain metastases at some time during the course of their disease. Patients who have the EGFRm form of NSCLC, which occurs in 10-15% of NSCLC patients in the US and Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. Approximately two-thirds of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the secondary mutation, T790M.

About Tagrisso
Tagrisso (osimertinib) 40mg and 80mg once daily oral tablet has been approved in over 45 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced non-small cell lung cancer (NSCLC). Eligibility for treatment with Tagrisso is dependent on confirmation that the EGFR T790M mutation is present in the tumour.

Tagrisso is a third generation, irreversible EGFR tyrosine kinase inhibitor designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations and to have activity in the central nervous system (CNS). Tagrisso is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.