publication date: Jan. 6, 2017

Drugs & Targets

AACR project GENIE releases cancer genomic data set

The American Association for Cancer Research announced the first public release of cancer genomic data aggregated through its initiative known as AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at eight international institutions, making it among the largest fully public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including data on nearly 3,000 patients with lung cancer, more than 2,000 patients with breast cancer, and more than 2,000 patients with colorectal cancer. The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR website or downloaded directly from Sage Bionetworks.

“These data were generated as part of routine patient care and without AACR Project GENIE they would likely never have been shared with the global cancer research community,” said Charles Sawyers, AACR Project GENIE Steering Committee chair, chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center, and a Howard Hughes Medical Institute investigator. “We are committed to sharing not only the real-world data within the AACR Project GENIE registry but also our best practices, from tips about assembling an international consortium to the best variant analysis pipeline, because only by working together will information flow freely and patients benefit rapidly.”

The data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act. They are derived from patients whose tumors were genetically sequenced as part of their care at one of the eight international institutions that participated in the first phase of AACR Project GENIE. Therefore, the genomic data are clinical grade.

The eight institutions participating in AACR Project GENIE phase 1 are:

  • Dana-Farber Cancer Institute;

  • Gustave Roussy Cancer Campus ;

  • The Netherlands Cancer Institute, on behalf of the Center for Personalized Cancer Treatment;

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

  • Memorial Sloan Kettering Cancer Center;

  • Princess Margaret Cancer Centre;

  • University of Texas MD Anderson Cancer Center; and

  • Vanderbilt-Ingram Cancer Center.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets a set of criteria can submit an application to become a project participant.


Strata Trial study launched with UNC, Alabama cancer centers

Strata Oncology today announced launch of the Strata Trial, a nationwide observational study providing no-cost tumor sequencing and clinical trial matching for 100,000 advanced cancer patients, to study the impact of tumor sequencing on clinical trial enrollment.

Strata Oncology completed collaboration agreements with its first two cancer center partners, University of North Carolina Lineberger Comprehensive Cancer Center and University of Alabama Comprehensive Cancer Center.

Participation in the Strata Trial enables the centers to offer tumor sequencing to all eligible advanced cancer patients at no cost, and to access Strata Oncology’s portfolio of affiliated pharma-sponsored clinical trials. To broaden regional access to the Trial, the agreements also provide for patient participation at the cancer centers’ regional affiliate hospitals.

In addition, Strata Oncology announced validation of its Strata next-generation sequencing Test and CLIA certification of its high-throughput cancer sequencing laboratory in Ann Arbor, MI. The company will provide access to the Strata NGS Test, under an IRB-approved screening protocol, to cancer patients at UNC Lineberger and UAB and their affiliate hospitals, with additional clinical partnerships to follow.


Foundation Medicine receives FDA approval as companion diagnostic

FoundationFocus CDxBRCA received FDA approval for use as a companion diagnostic to aid in identifying women with ovarian cancer.

It is a next generation sequencing test for qualitative detection of BRCA1 and BRCA2alterations in formalin-fixed paraffin-embedded ovarian tumor tissue. The FoundationFocus CDxBRCA assay detects sequence alterations in BRCA1 and BRCA2 genes.

Results of the test are used as an aid in identifying ovarian cancer patients for whom treatment with Rubraca (rucaparib) is being considered. If a patient is positive for any of the deleterious alterations specified in the BRCA1/2 classification, the patient may be eligible for treatment with Rubraca. This may help identify more women who could benefit from Rubraca therapy as compared to conventional testing methods that only identify germline BRCA1/2mutations. Germline-only BRCA1/2 testing identifies approximately half of all BRCA1/2 mutations.

Rubraca is a poly polymerase inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Foundation Medicine and Clovis Oncology closely collaborated on a regulatory strategy to develop FoundationFocus CDxBRCA in parallel with the development of Rubraca (rucaparib). Tissue samples taken from individuals with ovarian cancer who enrolled in rucaparib clinical trials were analyzed by Foundation Medicine utilizing comprehensive genomic profiling to identify biomarkers associated with a response to therapy.

These molecular signatures of response informed the development of FoundationFocus CDxBRCA, which was utilized in Clovis’ pivotal trial, ARIEL2, to identify patients and accelerate recruitment into the study. The companies filed concurrent pre-market approval and new drug application submissions with the FDA earlier this year.

With this FDA approval, FoundationFocus CDxBRCA is the first validated, tissue-based assay developed from the Quality Systems Regulations-compliant version of Foundation Medicine’s CGP assay, providing uniform analysis of all BRCA1/2 coding exons.

“These simultaneous approvals by the FDA represent a step forward for women with advanced ovarian cancer, an area where there is a tremendous need for effective therapeutic approaches and efficient ways to identify those most likely to respond to PARP inhibitor therapy,” said Michael Pellini, chief executive officer of Foundation Medicine. “This approval also represents a significant milestone for Foundation Medicine, one that underscores the quality and value of our molecular information solutions to inform patient care and to accelerate and streamline the therapeutic development programs of our biopharmaceutical partners.”


Ionis gets $28 million from AstraZeneca for new cancer drug

Ionis Pharmaceuticals Inc. announced that it has earned $28 million from AstraZeneca following AstraZeneca’s completion of IND-supporting studies and license of IONIS-KRAS-2.5, or AZD4785. IONIS-KRAS-2.5x is a Generation 2.5 antisense drug discovered by Ionis designed to directly target KRAS, one of the most frequently mutated genes in cancer.

IONIS-KRAS-2.5x will be the first drug to enter clinical development that directly targets KRAS, regardless of mutation type. AstraZeneca will be responsible for further developing and commercializing IONIS-KRAS-2.5.

Ionis and AstraZeneca are collaborating to discover and develop antisense drugs to treat cancer under a Collaboration, License and Development Agreement entered into in December 2012. The collaboration combines AstraZeneca’s experience and expertise in developing anti-cancer agents with Ionis’ antisense technology platform to broaden Ionis’ cancer franchise.

With the completion of the IND-supporting studies for IONIS-KRAS-2.5Rx, Ionis has received more than $85 million in upfront and milestone payments from its oncology collaboration with AstraZeneca and is eligible to earn additional milestone payments as the drug progresses in development as well as royalties on sales of IONIS-KRAS-2.5x if it is commercialized.

AstraZeneca is also evaluating, as part of the oncology collaboration, another drug to treat cancer, AZD9150 (IONIS-STAT3-2.5Rx), in combination with durvalumab, AstraZeneca’s investigational anti-PD-L1 antibody, in patients with head and neck cancer and in patients with diffuse large B-cell lymphoma. The two companies have also formed a collaboration to discover and develop antisense therapies for treating cardiovascular, metabolic and renal diseases.


MaxCyte, Washington University in St. Louis announce collaboration

MaxCyte Inc. and Washington University in St. Louis announced a collaboration to develop unique immunotherapy drug candidates based on MaxCyte’s proprietary cell engineering platform technology, CARMA.

CARMA allows simple and rapid manufacture of advanced cancer treatments that utilize a patient’s own immune system and is differentiated from traditional CAR therapy due to its use of mRNA to engineer immune cells delivered back into a patient. By utilizing transient expression via mRNA delivery, CARMA allows control over severe adverse effects, opening the high potency of CAR immunotherapies to a broader range of cancers than traditional CAR approaches.

John DiPersio, chief of the Division of Oncology at Washington University School of Medicine and deputy director of the Siteman Cancer Center, and members of his team will collaborate with MaxCyte to conduct preclinical research with a focus on developing a potential investigational CAR therapy targeting acute myeloid leukemia and other related blood cancers. Financial terms were not disclosed.


MD Anderson, Affimed collaborate on immunotherapy combination

MD Anderson and German-based Affimed N.V., announced an exclusive strategic clinical development and commercialization collaboration to evaluate Affimed’s TandAb technology in combination with MD Anderson’s natural killer cell product.

The technology to grow NK-cells from umbilical cord blood was developed at MD Anderson.

Collaborative studies will research, develop, and eventually commercialize novel oncology therapeutics resulting from this combination of products. MD Anderson will be responsible for conducting preclinical research activities aimed at investigating its NK-cells derived from umbilical cord blood in combination with Affimed’s lead NK-cell engager, the CD30- and CD16A-targeting TandAb AFM13. These are intended to be followed by a phase I study.

Affimed will fund research and development expenses for this collaboration and the agreement includes a provision for the potential expansion of the partnership. Affimed holds an option to exclusive worldwide rights to develop and commercialize any product developed under the collaboration.

AFM13 is a bispecific NK-cell TandAb simultaneously targeting CD16A on NK-cells and CD30 on tumor cells. AFM13 is designed to treat CD30-positive malignancies including Hodgkin lymphoma and T-cell lymphoma and is currently in phase II development in HL patients. Based on its safety profile, AFM13 is being developed both as monotherapy and in combination with other therapeutics such as Merck’s checkpoint inhibitor Keytruda.


Gradalis, Mount Sinai announce research alliance

Gradalis Inc. and the Icahn School of Medicine at Mount Sinai established a research alliance to advance the scientific understanding of the Gradalis Vigil Engineered Autologous Tumor Cell therapy.

Under the agreement, Gradalis will provide funding and clinical samples for studying the immune response to the therapy.

The research collaboration will be jointly headed by Gradalis’ Chief Scientific Officer John Nemunaitis and Seunghee Kim-Schulze, assistant professor of medicine and facility director, Human Immune Monitoring Core at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

The collaboration will span multiple clinical trials including the recently completed first in human study and ovarian phase 2A study. Additional collaboration efforts may be initiated to support ongoing registrational clinical trials in Ewing’s sarcoma and ovarian cancer, as well as trials exploring the combination of Vigil and PD-1/PDL-1 inhibitors in non-small cell lung cancer, melanoma and triple negative breast cancer.

With Vigil, a patient’s tumor cells are engineered with a plasmid carrying the gene vector for shRNA Furin and GMCSF to elicit a systemic T-cell directed immune response when administered to the patient through intradermal injections.


Phylogica, Genentech extend agreement

Phylogica Ltd. said Genentech has extended its exclusivity period for the research collaboration and license agreement to discover novel antibiotics utilizing Phylogica’s Phylomer drug discovery platform, including its proprietary cell penetrating peptide discovery technology.

A member of the Roche Group, Phylogica is a public Australian drug discovery company. Genentech is a member of the Roche Group.


Senhwa gets FDA orphan drug designation

Senhwa Biosciences Inc. of Taipei and San Diego received the orphan drug designation to CX-4945 for the treatment of cholangiocarcinoma.

CX-4945 is a novel small molecule drug that inhibits protein kinase CK2, the company said.

Orphan drug designation is granted by the FDA to novel drugs or biologics that treat rare diseases or conditions affecting fewer than 200,000 patients in the U.S. In the US, orphan drug status carries with it seven years of marketing exclusivity following FDA approval.

Under the agreement, Phylogica will receive a milestone payment of $2 million. Phylogica is eligible to receive research, development, and commercialization milestone payments totaling up to $142 million.

Oncotype DX included in AJCC staging criteria

The American Joint Committee on Cancer has incorporated the Oncotype DX test in its recently published Eighth Edition AJCC Cancer Staging Manual.

“For the first time, AJCC has added molecular signatures to complement the traditional anatomic features of the disease, transitioning cancer diagnosis and care to truly personalized medicine,” said Steven Shak, chief scientific officer, Genomic Health. “We believe this groundbreaking milestone will enhance physicians’ ability to deliver the excellent patient outcomes demonstrated across multiple prospective studies of the Oncotype DX test.”

Effective January 2018, the new AJCC Prognostic Stage Groups will add the Oncotype DX Breast Recurrence Score, hormonal status, and HER2 status to nodal status, tumor size, and tumor grade for staging breast cancer. For patients with node-negative disease or micrometastases in the nodes, a low Oncotype DX Recurrence Score (RS<11) classifies a patient as having the most favorable Prognostic Stage, regardless of tumor grade or tumor size (up to five centimeters).

As part of the implementation process, all AJCC partners, including the College of American Pathologists and the National Comprehensive Cancer Network, will develop and update protocols and tools to facilitate successful adoption of the required new staging system rules in 2018. The electronic version of the Eighth Edition AJCC Cancer Staging Manual is scheduled to be available the first quarter of 2017.

As stated in the AJCC publication, “Based on the best available evidence at this time, the Expert Panel determined that it was appropriate to incorporate multigene molecular profiling to incorporate the Oncotype DX score into staging for the subgroup of patients defined by Arm A of the TAILORx study. These patients should be staged according to the AJCC Prognostic Stage Groups. The findings for the ODX (Oncotype DX) test are supported by Level I Evidence (large-scale prospective clinical trial data).”

The results of the Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, led by the ECOG-ACRIN Cancer Research Group were published in The New England Journal of Medicine in 2015. Additionally, the Eighth Edition AJCC Cancer Staging Manual cites clinical outcomes data from tens of thousands of patients in the United States generated by the NCI Surveillance, Epidemiology, and End Results registry, demonstrating that patients with low Recurrence Scores have excellent breast cancer survival at five years.

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