NCI collaborates with Multiple Myeloma Research Foundation

On September 28, 2016 The National Cancer Institute (NCI) reported a collaboration with the Multiple Myeloma Research FoundationExit Disclaimer (MMRF) to incorporate MMRF’s wealth of genomic and clinical data about the disease into the NCI Genomic Data Commons (GDC), a publicly available database that promotes the sharing of genomic and clinical data among researchers and facilitates precision medicine in oncology (Press release, US NCI, SEP 28, 2016, View Source [SID:SID1234515490]). The MMRF, located in Norwalk, Connecticut, is the first nonprofit organization to donate information to the GDC, which will include data on more than 30,000 patients who have many other types of cancers by the end of the year. NCI is part of the National Institutes of Health.

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Multiple myeloma is the second most common blood cancer, but large amounts of genomic data about this disease and other cancers have not been readily accessible to the research community. At a meeting in Boston today, the Health Care Forum: War on CancerExit Disclaimer hosted by The Economist, leaders in the healthcare field discussed the benefits of this new partnership.

"Data sharing is essential to advancing cancer research, and I cannot overstate the value of the data that MMRF is providing — not only genomic data but also full clinical data as well," said Doug Lowy, M.D., NCI acting director. "Combining genomic and clinical information will create an invaluable resource for all researchers worldwide studying this disease who are working toward new, more effective treatments."

"The MMRF is a research and advocacy organization conducting clinical studies that incorporate whole-genome, whole-exome, and RNA sequencing into their study analyses," said Louis Staudt, M.D., Ph.D., director of NCI’s Center for Cancer Genomics. "The GDC gains power with each new submission, and the contribution of MMRF data will enable the discovery of potentially actionable and life-changing insights into multiple myeloma and its response to therapy that could be used by cancer researchers, doctors, and patients."

Launched earlier this year, the GDC allows researchers to submit genetic and clinical data, such as cancer imaging and histological data, and integrate these data with information on the molecular profiles of tumors as well as treatment responses. Importantly, all patient information in the GDC has been de-identified, meaning that personal information, such as addresses, Social Security numbers, and other possible identifiers, are not present — only crucial genetic data and key demographic information are available.

An important contribution to the GDC will be information from MMRF’s newest genomic study, Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass, NCT01454297). The trial has enrolled more than 1,150 patients to date and is currently the largest genomic and clinical study of this disease. African Americans represent about 18 percent of the patients enrolled CoMMpass, based on an interim analysis. The participation of African Americans in this study is significant given that multiple myeloma occurs about twice as often in African Americans than in whites.

Over the next eight years or longer, patients in CoMMpass will get a repeat biopsy and a new genomic analysis at each six-month checkup and/or at disease progression. Tumor samples are being collected and analyzed when possible at the time of any relapse. The genomic data from these analyses will be immediately deposited in the GDC, with an anticipated sample size of near 1,000 cases by the spring of 2017. New data will be deposited every six months at a minimum.

The MMRF will also share data from the 204-patient Towards a Genomic Understanding of Myeloma study, also known as the MMRF Multiple Myeloma Genomics Initiative. Through this initiative, whole genome sequencing of the myeloma genome was completed for the first time.

"GDC’s visualization tools and browsing capabilities will make the MMRF myeloma data more accessible and could help jumpstart research into this cancer," noted Staudt.

The GDC is a core component of the Cancer Moonshot and the President’s Precision Medicine Initiative, and it benefits from $70 million allocated to NCI to lead efforts in cancer genomics as part of the initiative.

Merrimack to Present Final Results of Phase 3 NAPOLI-1 Study at the European Society for Medical Oncology 2016 Congress

On September 28, 2016 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) reported it will present six posters from its systems-biology derived antibody engineering and nanotherapeutic portfolios at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress, October 7 – 11, 2016 in Copenhagen, Denmark (Press release, Merrimack, SEP 28, 2016, View Source [SID:SID1234515489]).

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Merrimack will present the final results of the Phase 3 NAPOLI-1 study in a poster discussion session and a NAPOLI-1 safety-over-time subset analysis in a separate poster session. The primary Phase 3 NAPOLI-1 data were the basis of the US Food and Drug Administration (FDA) and Taiwan FDA approvals of the ONIVYDE (irinotecan liposome injection) combination regimen in October 2015. It is also the basis of the European Union’s Committee for Medicinal Products for Human Use (CHMP) positive opinion issued in July 2016.

Additional ESMO (Free ESMO Whitepaper) 2016 poster presentations include an evaluation of MM-302’s potential for treating HER2-intermediate tumors as well as two trials-in-progress posters, both potentially registrational, for MM-302 and seribantumab, also known as MM-121. MM-302 is an investigational HER2-targeted liposomal encapsulation of doxorubicin from Merrimack’s antibody-directed nanotherapeutic platform, while seribantumab is Merrimack’s investigational anti-ErbB3 monoclonal antibody that targets heregulin-positive cancer cells within solid tumors.

Poster Discussion Session:

Final results of NAPOLI-1: A Phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy (Abstract 622PD)
Session Title: Gastrointestinal tumours, non-colorectal
Date/Time: October 8, 2016, 8:40 am – 8:50 am (CEST)
Location: Copenhagen
Poster Sessions:

Time course of selected treatment emergent adverse events (TEAEs) in NAPOLI-1: A Phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy (Abstract 693)
Session Title: Gastrointestinal tumours, non-colorectal
Date/Time: October 8, 2016, 1:00 pm – 2:00 pm (CEST)
Location: Hall E

Quantitative evaluation of HER2-mediated cellular uptake of the HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 suggests potential for treating HER2-intermediate tumors (Abstract 1560)
Session Title: Translational research
Date/Time: October 10, 2016, 1:00 pm – 2:00 pm (CEST)
Location: Hall E

HERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and T-DM1 (Abstract 315TIP)
Session Title: Breast cancer, locally advanced and metastatic
Date/Time: October 10, 2016, 1:00 pm – 2:00 pm (CEST)
Location: Hall E

SHERLOC: A Phase 2 study of seribantumab (MM-121) in combination with docetaxel or pemetrexed versus docetaxel or pemetrexed alone in patients with heregulin positive (HRG+), locally advanced or metastatic non-small cell lung cancer (NSCLC) (Abstract 1296TIP)
Session Title: NSCLC, metastatic
Date/Time: October 8, 2016, 1:00 pm – 2:00 pm (CEST)
Location: Hall E

EISAI TO PRESENT LATEST DATA ON LENVATINIB AND ERIBULIN AT ESMO CONGRESS 2016

On September 29, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that a series of abstracts highlighting the latest clinical and pre-clinical data on lenvatinib mesylate (selective inhibitor of receptor tyrosine kinases (RTKs) with a novel binding mode, product name: Lenvima/Kisplyx, "lenvatinib") and eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: Halaven, "eribulin") will be presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2016, taking place in Copenhagen, Denmark, from October 7 – 11 (Press release, Eisai, SEP 28, 2016, View Source [SID:SID1234515488]).

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For lenvatinib, six abstract poster presentations (including health economics and outcome research data) are to be given at the meeting with the main presentations featuring the latest data from a Phase Ib trial of lenvatinib in combination with the immune checkpoint inhibitor pembrolizumab in patients with selected solid tumors as well as an analysis of the responses in specific metastases following treatment with lenvatinib from the results of the Phase III SELECT Study.

For eribulin, an abstract poster presentation on a subgroup analysis in leiomyosarcoma (LMS) patients from a Phase III study (Study 309) in patients with advanced liposarcoma (LPS) and LMS is also scheduled to be given at the meeting.

Eisai positions oncology as a key franchise area. The company will continue to create innovation in the development of new drugs based on cutting-edge cancer research, and in doing so seeks to make further contributions to address the diversified needs of, and increase the benefits provided to, patients and their families as well as to healthcare providers.

Major Eisai abstracts accepted for presentation at this year’s ESMO (Free ESMO Whitepaper) meeting include:
Product Abstract title and scheduled presentation date and time (local time)
Lenvatinib

Abstract No: 2038 Responses in Specific Metastases Following Treatment with Lenvatinib: Results from the Phase III SELECT Study
Poster Presentation | October 9 (Sun), 13:00-14:00
Lenvatinib

Abstract No: 1608 Phase II study of lenvatinib (LEN) in patients (pts) with RET fusion–positive adenocarcinoma of the lung
Poster Presentation | October 9 (Sun), 14:45-16:15
Lenvatinib

Abstract No: 1779 A Phase Ib Trial of lenvatinib plus pembrolizumab in patients with selected solid tumors

Poster Presentation | October 9 (Sun), 16:30-17:30
Lenvatinib

Abstract No: 2008 Lenvatinib mesilate enhanced antitumor activity of PD-1 blockade agent by potentiating a Th1 immune response
Poster Presentation | October 9 (Sun), 16:30-17:30
Lenvatinib

Abstract No: 1284 The antitumor activity of lenvatinib (LEN) in combination with everolimus (EVE) in human renal cell carcinoma (RCC) xenograft models is dependent on VEGFR and FGFR signaling
Poster Presentation | October 10 (Mon), 13:00-14:00
Lenvatinib

Abstract No: 2616 Understanding real world treatment patterns, healthcare resource utilization (HRU) and costs among metastatic renal cell carcinoma (mRCC) patients
Poster Presentation | October 9 (Sun), 13:00-14:00
Eribulin

Abstract No: 1879 Subgroup analysis in leiomyosarcoma (LMS) patients (pts) from a Phase III, open-label, randomized study of eribulin (ERI) versus dacarbazine (DTIC) in pts with advanced Liposarcoma (LPS) and LMS
Poster Presentation | October 10 (Mon), 11:00-12:00
(Note) SELECT Study: Study of E7080 "LEnvatinib" in Differentiated Cancer of the Thyroid

Genomic Health Reinforces Global Leadership in Genomic-based Diagnostics with Presentation of Nine Personalized Medicine Studies Conducted in Six Countries at ESMO 2016 Congress

On September 28, 2016Genomic Health, Inc. (Nasdaq: GHDX) reported that the company will present results from nine studies at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress, which will take place October 7-11 at the Bella Center in Copenhagen, Denmark (Press release, Genomic Health, SEP 28, 2016, View Source [SID:SID1234515482]). The results will include:

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Analytical validation study results for the recently launched Oncotype SEQ Liquid Select test. Oncotype SEQ is the first non-invasive liquid biopsy test that the company is delivering through its Oncotype IQ Genomic Intelligence Platform.
Two presentations highlighting updated prospective outcomes from a large population-based observational study based on the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI). The primary SEER Registry study results, published in Nature Partner Journals Breast Cancer, demonstrated that the Oncotype DX Breast Recurrence Score accurately predicted prospective patient outcomes in more than 44,500 patients, including those with node-negative and node-positive breast cancer. The updated results to be presented at ESMO (Free ESMO Whitepaper) will include an additional year of patient data and an additional year of follow-up for patients included in the original study.
New prospective outcomes data on the Oncotype DX Breast Recurrence Score from a multi-center study in node-positive disease from Clalit Health Services, the largest health maintenance organization in Israel.
Five international studies demonstrating the value of the Oncotype DX Breast Recurrence Score on treatment decisions in Canada, the Czech Republic, Italy and Spain. These studies include new prospective clinical utility evidence for node-positive disease and results on the clinical impact of Oncotype DX beyond immunohistochemistry for Ki-67.
The ESMO (Free ESMO Whitepaper) abstracts are now available at www.esmo.org. Following are details for each presentation (all times are in Central European Summer Time):

Friday, October 7

Abstract: 146 O
Proffered Paper Session: "Outcome disparities by age and 21-gene recurrence score (RS) result in hormone receptor positive (HR+) breast cancer (BC)"
Author: S. Shak, M.D.
Location: Stockholm
Time: 16:00 – 17:30
Saturday, October 8

Abstract: 147 PD
Poster Discussion Session: "First prospectively-designed outcome study in estrogen receptor (ER)+ breast cancer (BC) patients (pts) with N1mi or 1-3 positive nodes in whom treatment decisions in clinical practice incorporated the 21-gene Recurrence Score result"
Authors: S. Stemmer, M.D.
Location: Berlin
Time: 15:00 – 16:00

Abstract: 150 PD
Poster Discussion Session: "Breast cancer-specific survival in > 4,600 patients with lymph node-positive (LN+) hormone receptor-positive (HR+) invasive breast cancer (BC) and 21-gene Recurrence Score (RS) results in the SEER registries"
Authors: D.P. Miller
Location: Berlin
Time: 15:00 – 16:00
Monday, October 10

Abstract: 175 P
Poster Display: "First prospective multicenter Italian study on the impact of the 21-gene Recurrence Score (RS) in adjuvant clinical decisions for ER+/HER2- early breast cancer patients"
Author: M.V. Dieci
Location: Hall E
Session Time: 13:00 – 14:00

Abstract: 181 P
Poster Display: "Budget impact analysis of the 21-gene assay (Oncotype DX Breast Cancer) for the breast cancer treatment in the Basque country"
Author: Toribio, M.D.
Location: Hall E
Session Time: 13:00 – 14:00

Abstract: 177 P
Poster Display: "The impact of the 21-gene assay in the Czech Republic on adjuvant chemotherapy (CT) recommendations and costs in estrogen receptor positive (ER+) early stage breast cancer (ESBC) patients with grade 2 tumors and risk factors"
Author: K. Petrakova, M.D., Ph.D.
Location: Hall E
Session Time: 13:00 – 14:00

Abstract: 180 P
Poster Display: "Use of Oncotype DX Recurrence Score (RS) reduces chemotherapy (CT) beyond treatment decisions using Ki67-based determinations of luminal A and B breast cancer subtypes: A retrospective study in the Spanish population"
Author: L. Garcia-Estevez, M.D.
Location: Hall E
Session Time: 13:00 – 14:00

Abstract: 183 P
Poster Display: "Prospective evaluation of the impact of the 21-gene Recurrence Score assay on adjuvant treatment decisions for women with node-positive breast cancer in Ontario, Canada"
Author: S. Torres, M.D.
Location: Hall E
Session Time: 13:00 – 14:00

Abstract: 1162 P
Poster Display: "Analytical performance of a new liquid biopsy mutation panel for detection of clinically actionable variants"
Author: C. Svedman, M.D.
Location: Hall E
Session Time: 13:00 – 14:00

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. With more than 600,000 patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeDX.com, www.mybreastcancertreatment.org and www.myprostatecancertreatment.org.

TRACON PHARMACEUTICALS ANNOUNCES A STRATEGIC LICENSING COLLABORATION FOR TWO JANSSEN ONCOLOGY ASSETS AND A $5 MILLION EQUITY INVESTMENT FROM JOHNSON & JOHNSON INNOVATION – JJDC, INC.

On September 28, 2016 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age‐related macular degeneration and fibrotic diseases, reported a strategic licensing collaboration with Janssen Pharmaceutica N.V. (Janssen) for two novel oncology assets from Janssen’s early development portfolio, with Janssen retaining certain rights to potentially reacquire the programs (Press release, Tracon Pharmaceuticals, SEP 28, 2016, View Source;p=irol-newsArticle&ID=2206472 [SID:SID1234515481]). Johnson & Johnson Innovation facilitated the collaboration. Johnson & Johnson Innovation – JJDC, Inc. (JJDC) also made a $5 million equity investment in TRACON through the purchase of common stock at a price of $5.95 per share.

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Key Elements of the Transaction:

The transaction grants TRACON the rights to develop two Janssen oncology programs: TRC253 (formerly JNJ-63576253), a novel small molecule high affinity competitive inhibitor of wild type androgen receptor (AR) and multiple AR mutations that confer drug resistance, which is intended for the treatment of men with prostate cancer, and TRC694 (formerly JNJ-64290694), a novel, potent, orally bioavailable inhibitor of NF-kB inducing kinase (NIK), which is intended for the treatment of patients with hematologic malignancies, including myeloma.

TRC253 has completed IND-enabling studies and TRACON expects to initiate a Phase 1/2 proof of concept (POC) clinical study in the first half of 2017. Following completion of the initial POC study, Janssen will have an exclusive option to reacquire full rights to TRC253 for an upfront payment of $45 million to TRACON, and obligations to pay regulatory and commercialization milestones totaling up to $137.5 million upon achievement of specified events and a low single-digit royalty. If Janssen does not exercise its exclusive option to reacquire the program, TRACON would then retain worldwide development and commercialization rights to the program and would be obligated to pay Janssen a total of up to $45 million in development and regulatory milestones upon achievement of specified events, in addition to a low single digit royalty.

TRC694 is currently in preclinical development and TRACON expects to file an Investigational New Drug (IND) Application in 2018, following completion of additional preclinical studies. Upon completion of an initial clinical POC study, or at any time prior thereto, Janssen will have a right of first negotiation to reacquire the program on terms to be negotiated between the parties. If Janssen does not exercise the negotiation right or the parties cannot agree to terms following negotiations, and if TRACON continues development of TRC694, TRACON would be obligated to pay Janssen development and regulatory milestones totaling up to $60 million upon achievement of specified events and a low single-digit royalty.
"We are excited to enter into this innovative transaction with Janssen and Johnson & Johnson Innovation, and for the potential upside it provides our shareholders," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "This agreement expands our portfolio of potential first-in-class oncology therapies and leverages our existing drug development expertise. It also creates incremental opportunities for near-term non-dilutive funding and long-term value creation that complement our ongoing clinical development efforts with TRC105, our lead late-stage product candidate. Additionally, JJDC’s $5 million equity investment strengthens our balance sheet and is expected to offset the development expenses associated with these programs over the next 12 months."

About TRC253 (formerly JNJ-63576253)

TRC253 is a novel, orally bioavailable small molecule discovered and developed by Janssen that is a potent, high affinity competitive inhibitor of the androgen receptor (AR). TRC253 is also a pan-inhibitor of multiple AR mutations, including the F876L mutation, and is under development for the treatment of men with prostate cancer. The AR F876L mutation results in an alteration in the ligand binding domain that confers resistance to current AR inhibitors. IND-enabling studies have been completed for TRC253 and TRACON expects to initiate clinical development for the product candidate in the first half of 2017, following the completion of technology transfer from Janssen.

Activation of the AR is crucial for the growth of prostate cancer at all stages of the disease. Therapies targeting the AR have demonstrated clinical efficacy by extending time to disease progression, and in some cases, the survival of patients with metastatic castration-resistant prostate cancer. However, resistance to these agents is often observed and several molecular mechanisms of resistance have been identified, including amplification, overexpression or mutation of the AR.

TRC253 is intended to address resistance mechanisms to current AR inhibitors by specifically targeting mutations in the AR ligand binding domain. TRC253 also potently inhibits signalling through the wild type AR. These susceptible AR mutations have been identified using circulating tumor DNA assays, potentially allowing for selected patient biomarker-directed therapy.

About TRC694 (formerly JNJ-64290694)

TRC694 is a novel, potent, orally bioavailable inhibitor of NF-kB inducing kinase (NIK) with the potential to be first-in-class and was discovered by Janssen. In pre-clinical studies, TRC694 selectively repressed P52/RelB mediated non-canonical NF-kB gene expression and inhibited NIK and TRAF3 mutant cell line proliferation in vitro and tumor growth in vivo. TRACON anticipates completing development of a companion diagnostic to enable patient-directed therapy and submitting an IND for TRC694 in 2018.

Genetic alterations leading to stabilization of NIK are found in a subset of B-cell malignancies: multiple myeloma, mantle-cell lymphoma (MCL, associated with ibrutinib), diffuse large B-cell lymphoma (DLBCL), cHL and CLL.

About TRC105 (carotuximab)

TRC105 (carotuximab) is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumor types in combination with VEGF inhibitors. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis. For further information about the clinical trials, please visit TRACON’s website at View Source