On December 12, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that characterizations of T cell receptor candidates which it has licensed under the Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health (NIH) have been published in the December 8, 2016 New England Journal of Medicine (NEJM) (Press release, Kite Pharma, DEC 12, 2016, View Source [SID1234517047]).

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The research, led by Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch at NCI’s Center for Cancer Research, and a scientific collaborator with Kite, describes a patient with KRAS mutant metastatic colorectal cancer who was successfully treated with T cells that are reactive to KRAS G12D mutation. This work follows previously reported treatment of a patient with advanced cholangiocarcinoma with T cells targeting a mutated erbb2 interacting protein.

"We are very excited to see the results of this landmark study conducted by Dr. Rosenberg and his team at the NCI. These findings represent proof of concept that T-cell technology directed against neoantigens can be utilized to treat solid tumors," said David Chang, M.D., Ph.D., Executive Vice President, Research and Development, and Chief Medical Officer of Kite.

As published in the NEJM publication, mutations in the KRAS gene are thought to drive 95 percent of all pancreatic cancers and 45 percent of all colorectal cancers. The G12D mutation is the most common KRAS mutation and is estimated to occur in more than 50,000 new cases of cancer in the United States each year.

In September 2016, Kite announced that it had entered into an exclusive, worldwide license with NIH for intellectual property related to multiple TCR-based product candidates for the treatment of tumors expressing mutated KRAS antigens. These TCR product candidates were developed in the laboratories of Steven A. Rosenberg, M.D., Ph.D., and James C. Yang, M.D., of the NCI.

On December 12, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported study findings relating to the prognostic value of the PAM50-based Prosigna Breast Cancer Gene Signature Assay in treating breast cancer that were presented at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) (Press release, NanoString Technologies, DEC 12, 2016, View Source [SID1234517041]). Investigators retrospectively evaluated and compared the performance of four multigene expression profiles to predict the risk of Distant Recurrence (DR) in the same large dataset of more than 800 patients from the TransATAC study. These signatures included Prosigna, Oncotype DX, EndoPredict and Breast Cancer IndexSM.

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For post-menopausal women with node-negative, hormone receptor-positive, HER2-negative early stage breast cancer, the study found that Prosigna provided the most accurate prognostic information of all four multigene expression profiles tested as measured by the statistical measure known as the likelihood ratio. The study further found that Prosigna also provided the most accurate differentiation between low and high risk patients as compared to the other genomic tests. Low-risk women as identified by Prosigna had a 3% risk of DR over 10 years, the lowest rates of DR for all genomic tests that were studied. In contrast, high-risk women as identified by Prosigna had on average a 33% chance of distant recurrence by 10 years.

These results support the conclusions of the 2016 evidence-based ASCO (Free ASCO Whitepaper) guidelines that multi-gene expression signatures provide clinical utility for selection of low risk patients who may be spared adjuvant chemotherapy based upon their outcomes when treated with hormone therapy alone. Those guidelines gave a strong recommendation for Prosigna, equivalent to the recommendation given for Oncotype Dx and stronger than other tests evaluated by the guideline committee.

Additional results from the study demonstrated the potential clinical utility of Prosigna for informing the duration of endocrine therapy by accurately assessing the risk of a patient’s cancer recurring between five and 10 years after diagnosis. In node-negative patients, Prosigna provided the most prognostic information between 5 and 10 years after diagnosis as measured by the likelihood ratio. Low-risk women as identified by Prosigna had a 1.4% risk between years 5 and 10, the lowest rates of DR for all genomic tests that were studied.

"This important data demonstrates the ability of Prosigna to identify a low risk group of women for whom adjuvant chemotherapy following surgery and extended endocrine therapy in years 5-10 following diagnosis may be of limited benefit," said Dr. Aleix Prat, MD, Ph.D., from Hospital Clinic in Barcelona, Spain, who was not an investigator on the study.

"These results further validate the clinical utility of Prosigna as a superior second generation breast cancer assay that provides oncologists and patients the critical information they need to make informed decisions about their treatment options," stated Brad Gray, president and chief executive officer of NanoString Technologies.

Results of the TransATAC analysis were presented on Friday December 9th by Ivana Sestak Ph.D. in SABCS abstract S6-05, titled Comprehensive comparison of prognostic signatures for breast cancer in TransATAC. Prosigna’s performance as part of the TransATAC study has been previously published in the Journal of Clinical Oncology (View Source) and the Journal of the National Cancer Institute (View Source).

About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System
The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is 510(k) cleared for use on the nCounter Dx Analysis System, and is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand, Argentina, Thailand, South Africa, Turkey and Hong Kong. In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:

(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

Other uses of Prosigna or the PAM50 panel in studies as described in this press release are for Investigational Use Only, or Research Use Only.

On December 12, 2016 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the abstract titled "Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions" has been accepted for oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress, taking place December 16-19, 2016 in Singapore (Press release, Loxo Oncology, DEC 12, 2016, View Source [SID1234517040]). Data from this trial were last presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2016. The presentation will include an efficacy and durability update for enrolled patients with TRK fusions.

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The schedule for the presentation is as follows:

Presentation Session Date & Time: December 18, 2016, 4:30 p.m. to 6:00 p.m. SGT
Title: Clinical safety and activity from a phase 1 study of LOXO-101, a selective
TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions
Abstract Number: 150O
Session: Developmental Therapeutics, Proffered Paper Session (oral presentation)
Presenter: Todd Bauer, M.D., Associate Director, Drug Development; Principal Investigator, Sarah Cannon Research Institute

On December 12, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that the results of an interim analysis of a global Phase Ib/II clinical study (Study 218) of its in-house discovered and developed anticancer agent eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: Halaven, "eribulin") in combination with the anti-PD-1 antibody pembrolizumab developed by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the U.S. and Canada), in patients with metastatic triple-negative breast cancer have been presented at the 39th Annual San Antonio Breast Cancer Symposium held from December 6 to 10, 2016 (Press release, Eisai, DEC 12, 2016, View Source [SID1234517039]). Development of this combination regimen is being conducted jointly under the cooperation of both companies.

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Study 218 is a Phase Ib/II clinical study which examined the activity and safety of eribulin in combination with pembrolizumab in 95 patients with metastatic triple-negative breast cancer previously treated with 0 – 2 lines of chemotherapy in the metastatic setting. The primary objective of the Phase Ib part was safety and tolerability, and the primary objective of the Phase II part was objective response rate (ORR).

This presentation reported on the results of an interim analysis of 39 evaluable patients out of the 89 patients enrolled in the study as of July 2016. Eribulin (1.4 mg/m2 intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) were administered to patients over 21 day cycles. From the results of the study, ORR was 33.3% (1 patient experienced a complete response and 12 patients experienced a partial response). In addition, the ORR was similar between PD-L1 positive and negative cohorts.

In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 35%) in patients treated with the combination regimen were fatigue, nausea, peripheral neuropathy, neutropenia and alopecia, with Grade 3 or higher Treatment-Emergent Adverse Events (TEAEs) observed in 66.7% of patients. The most common Grade 3 or higher TEAEs (incidence greater than or equal to 7%) observed were neutropenia (30.8%) and fatigue (7.7%).

Eribulin is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Recent non-clinical studies showed that eribulin is associated with increased vascular perfusion and permeability in tumor cores.1 Eribulin promotes the epithelial state and decreases the capacity of breast cancer cells to migrate and invade.2 It was first approved for use in the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved for use in the treatment of patients with breast cancer in over 60 countries including Japan and countries in Europe, the Americas and Asia.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. As exemplified by this combination regimen, Eisai remains committed to providing further clinical evidence for eribulin aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

*Please refer to the following notes for the approved indications in the United States, Japan and Europe

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

< Notes to editors >

1. About eribulin mesylate (product name: Halaven, "eribulin")
Eribulin is a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, recent non-clinical studies showed that eribulin is associated with increased vascular perfusion and permeability in tumor cores.1 Eribulin promotes the epithelial state and decreases the capacity of breast cancer cells to migrate and invade.2

Eribulin was first approved for use in the treatment of metastatic breast cancer in the United States in November 2010. Eribulin is currently approved for use in the treatment of breast cancer in over 60 countries worldwide, including Japan and countries in Europe, the Americas and Asia.
Furthermore, eribulin was first approved as a treatment for liposarcoma in the United States in January 2016, and is also approved for liposarcoma in countries in Europe and soft tissue sarcoma in Japan.

Specifically, eribulin is approved for the following indications.
In the United States for the treatment of patients with:
Metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.
In Japan for the treatment of patients with:
Inoperable or recurrent breast cancer
Soft tissue sarcoma
In Europe for the treatment of adult patients with:
Locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.
Unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.
2. About the Phase Ib/II Study (Study 218)
Study 218 is a multicenter, single-arm, open-label Phase 1b/II clinical study which examined the activity and safety of eribulin in combination with pembrolizumab in 95 patients (12 patients for the Phase Ib part, 83 patients for the Phase II part) with metastatic triple-negative breast cancer previously treated with 0-2 lines of chemotherapy in the metastatic setting. Eribulin (1.4 mg/m2 intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) were administered to patients over 21 day cycles. The primary objective of the Phase Ib part was safety and tolerability, and the primary objective of the Phase II part was ORR. Progression-free survival was assessed as a secondary objective.

In this interim analysis of 39 patients, 22 patients were previously treated with 1 to 2 lines of chemotherapy in the metastatic setting. The ORR was similar between PD-L1 positive (17 patients, ORR 29.4%) and negative (18 patients, ORR 33.3%) cohorts and it was 50% for PD-L1 unknown cohorts. Pembrolizumab alone demonstrated the tendency to increase the antitumor activity with PD-L1 positive in triple-negative breast cancer patients (KEYNOTE-012 study)3
In this study, eribulin in combination with pembrolizumab is expected to show similar antitumor activity regardless of PD-L1 status.

3. About triple-negative breast cancer
Triple-negative breast cancer is a type of breast cancer where the cancer cells tested negative for expression of estrogen receptors, progesterone receptors and HER-2 receptors. Since the tumor cells lack the necessary receptors, common treatments like hormone therapy and drugs that target HER-2 are ineffective. This remains a disease with significant unmet medical need. Therefore, the development of new medicines is necessary to advance the treatment of triple-negative breast cancer.

4. About non-clinical research related to the mechanism of action for eribulin in combination with pembrolizumab
Eribulin contributes to maintaining or increasing the activity of cytotoxic T lymphocytes (CTLs), which play a leading role in attacking cancer cells, via reduction of immune suppressive Treg cells and M2 tumor macrophages4. The anti-PD-1 antibody pembrolizumab maintains or activates CTLs via its immune-checkpoint blockade. Eribulin in combination with pembrolizumab is expected to work synergistically in cancer immunotherapy.