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Bristol-Myers Squibb Enters Collaboration to Leverage Foundation Medicine’s Molecular Information Platform to Identify Predictive Biomarkers Across Multiple Tumor Types and Immunotherapy Agents

On March 30, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Foundation Medicine (NASDAQ:FMI) reported a collaboration that leverages Foundation Medicine’s comprehensive genomic profiling and molecular information solutions to identify predictive biomarkers such as Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) in patients enrolled across clinical trials investigating Bristol-Myers Squibb’s cancer immunotherapies (Press release, Bristol-Myers Squibb, MAR 30, 2017, View Source [SID1234518330]). Biomarkers can be used to characterize a tumor and the tumor microenvironment, which may reveal immune-related mechanisms predictive of how a patient may respond to immunotherapy.

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Cancer immunotherapy works by helping the immune system mount an anti-cancer response, a process that depends in part on the recognition of cancer-specific proteins called neoantigens. Higher levels of tumor mutations have been shown to correlate to the number of neoantigens, and therefore may help identify patients more likely to respond to cancer immunotherapies. Foundation Medicine’s approach utilizing its FoundationOne assay combines comprehensive genomic profiling with its advanced and proprietary algorithms to measure biomarkers, including TMB and MSI, without the need for whole exome sequencing.

"Translational medicine research is critical to further our understanding of cancer biology and to identify which patient populations are most likely to derive benefit from our Immuno-Oncology agents," said Fouad Namouni, M.D., head of Development, Oncology, Bristol-Myers Squibb. "We believe this collaboration with Foundation Medicine will help us better understand the relation of genomic approaches to immunotherapy efficacy across a number of different tumor types and immunotherapy agents."

"Cancer immuno-therapy is evolving rapidly, and biopharmaceutical companies and practicing oncologists alike may benefit from a reliable, validated, comprehensive view of mutational burden and genomic alterations to make the most informed care decisions," said Melanie Nallicheri, chief business officer and head, Biopharma for Foundation Medicine. "Our collaboration with Bristol-Myers Squibb highlights the potential value of our molecular information platform to the biopharma industry for its ability to inform, to reduce risk and to accelerate clinical development in this high growth and highly competitive oncology field."

Kite to Present Two Plenary Presentations from the ZUMA-1 Pivotal Trial of Axicabtagene Ciloleucel at the 2017 American Association of Cancer Research Annual Meeting

On March 20, 2017 Kite Pharma, Inc. (Nasdaq:KITE) reported new data presentations from multiple studies related to its lead investigational candidate, axicabtagene ciloleucel, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington D.C., April 1-5, 2017 (Press release, Kite Pharma, MAR 30, 2017, View Source [SID1234518324]). Kite will also present pre-clinical data relating to KITE-585, the company’s fully human anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell product candidate. The full text for clinical trial abstracts will be available online March 31, 2017, at 4:30 p.m. Eastern Time, through the AACR (Free AACR Whitepaper) website at www.aacr.org.

"We are excited to present the primary analysis of ZUMA-1. The results demonstrate the promise of anti-CD19 CAR T-cell therapy to transform treatment of B-cell malignancies," said David Chang, M.D., Ph.D., Executive Vice President, Research and Development, and Chief Medical Officer. "We intend to apply the learnings from ZUMA-1, as well as our internal clinical development and manufacturing expertise, to accelerate the development of some of our most promising pipeline candidates such as KITE-585 into the clinic later this year."

Oral Presentations

Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axicel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL)

Abstract # CT019
Presenter: Frederick L. Locke, M.D., Moffitt Cancer Center, Tampa, FL
Session: Immuno-oncology Biomarkers in Clinical Trials Plenary Session
Sunday, April 2, 2017: 4:05-4:14 PM EDT; Hall D-E, Level 2
Immune signatures of cytokine release syndrome and neurologic events in a multicenter registrational trial (ZUMA-1) in subjects with refractory diffuse large B cell lymphoma treated with axicabtagene ciloleucel (KTE-C19)

Abstract # CT020
Presenter: Frederick L. Locke, M.D., Moffitt Cancer Center, Tampa, FL
Session: Immuno-oncology Biomarkers in Clinical Trials Plenary Session
Sunday, April 2, 2017: 4:14-4:24 PM EDT; Hall D-E, Level 2
Polyfunctional anti-CD19 CAR T cells determined by single-cell multiplex proteomics associated with clinical activity in patients with advanced non-Hodgkin’s lymphoma

Abstract # 2990
Presenter: John M. Rossi, M.S., Kite Pharma
Session: Clinical Research, Clinical Biomarkers
Monday, April 3, 2017: 4:05-4:20 PM EDT; Room 151, Level 1
Development of KITE-585: A fully human BCMA CAR T-cell therapy for the treatment of multiple myeloma

Abstract # 4979
Presenter: Gregor B. Adams, Ph.D., Kite Pharma
Session: Immunology: Adoptive Cellular Therapy for Cancer
Tuesday, April 4, 2017: 3:35-3:50 PM EDT; Ballroom A-B, Level 3
Poster Presentations

Selectivity and specificity of engineered T cells expressing KITE-585, a chimeric antigen receptor targeting B-cell maturation antigen (BCMA)

Abstract # 2135
Presenter: Tassja Spindler, Kite Pharma
Session: Experimental and Molecular therapeutics: New Targets 2
Monday, April 3, 2017: 1:00-5:00 PM EDT; Halls A-C, Poster Section 6
About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

About KITE-585

KITE-585 is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the B cell maturation antigen (BCMA), a protein expressed on the cell surface of multiple myelomas (MM), and redirect the T cells to kill cancer cells. In 2016, there were an estimated 30,330 new cases of MM and 12,650 disease related deaths in the US1. Current treatments, including multi-therapy combinations, require chronic care and most patients will eventually relapse2. Kite expects to file an Investigational New Drug Application (IND) for KITE-585 in 2017.

Ignyta Announces Peer-Reviewed Publication of Activity of a TRK Inhibitor in a Primary Brain Tumor: Successful Treatment of Glioneuronal Tumor With Pan-TRK, CNS-Active Inhibitor Entrectinib Published in Precision Oncology

On March 30, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported data demonstrating the successful treatment with entrectinib – Ignyta’s investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor TRK, ROS1 or ALK fusions – of a patient with a primary brain tumor harboring an NTRK1 fusion (Press release, Ignyta, MAR 30, 2017, View Source [SID1234518323]).

The study, exploring genetic alterations associated with glioneuronal tumors, was led by researchers at Massachusetts General Hospital and was published in Precision Oncology. Researchers discovered novel oncogenic fusions involving members of the NTRK gene family in three out of 26 patients evaluated, and reported that in a patient with a BCAN-NTRK1 fusion, treatment with entrectinib resulted in a 60 percent regression in tumor size and the resolution of clinical symptoms that was maintained for 11 months on treatment. Entrectinib is currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2.

"We are pleased to see the CNS activity of entrectinib demonstrated in this peer-reviewed publication in Precision Oncology, which highlights the need for CNS-active compounds to effectively treat CNS neoplasms, as well as other solid tumors with a propensity to metastasize to the brain," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "This robust activity of entrectinib in a patient with a primary brain tumor builds on the rapid and durable anti-tumor activity we’ve seen with this compound across other TRK, ROS1, or ALK solid tumors across multiple histologies and complements the 71% RECIST ORR (five out of seven patients) demonstrated in patients with extracranial tumors that had metastasized to the brain in our Phase 1 studies. Entrectinib is the only TRK inhibitor to have demonstrated RECIST responses in patients with CNS disease and the only TRK inhibitor to have a peer-reviewed publication on its activity in primary brain tumors."

Data presented in the study characterized a cohort of 26 glioneuronal tumors, which identified, through in-depth genomic analysis, BRAF mutations in 34 percent of tumors and oncogenic fusions in 30 percent of tumors. Further, researchers identified three tumors in the cohort that contained fusions involving members of the NTRK gene family, including one patient harboring a BCAN-NTRK1 fusion. Based on previous clinical results, therapeutic intervention for the patient harboring the NTRK1 fusion was pursued, and entrectinib was selected due to its CNS activity. Following subtotal surgical resection and confirmation of the tumor’s specific genetic alteration, the patient was enrolled in the Phase 1 dose-escalation trial of entrectinib (NCT02097810). The patient received entrectinib daily for 11 months and experienced lower extremity edema as the only documented side effect related to therapy. Analysis after nine months of treatment showed a 60 percent reduction in the size of the tumor, as well as improvement in vision-related symptoms. The patient was taken off of treatment after 11 months due to a gradual worsening of vision and tumor size. Based on the results of the study, we believe NTRK fusions should be considered an actionable target for glioneuronal tumor treatment.

Phase II Study of Daratumumab in Non-Hodgkin’s Lymphoma Will Not Proceed to Stage 2 of Trial

On March 30, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its collaboration partner for daratumumab, Janssen Biotech, Inc., has decided not to initiate stage 2 of the Phase II study (CARINA, LYM2001) of daratumumab in three types of relapsed or refractory non-Hodgkin’s lymphoma (NHL) (Press release, Genmab, MAR 30, 2017, View Source [SID1234518322]). The study will not proceed to stage 2 as a data review showed that two cohorts of the study, investigating the use of daratumumab monotherapy in relapsed or refractory patients with follicular lymphoma (FL), and with diffuse large B-cell lymphoma (DLBCL) did not reach the predefined futility thresholds of overall response rates (ORR) of 50%, and 30%, respectively. In the third cohort in the study, patients with mantle cell lymphoma (MCL), ORR was not evaluable due to slow recruitment, driven by the aggressive nature of the disease in its final stages. This has no impact on other ongoing or planned studies with daratumumab.

"While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue. Daratumumab is still being investigated in a number of indications including multiple myeloma and other hematological cancers such as NK/T-cell lymphoma and myelodysplastic syndrome as well as in solid tumors," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CARINA LYM2001 study
The Phase II study (NCT02413489) is a three arm (DLBCL, FL, MCL), open-label multicenter study, which planned to enroll up to 210 patients in 2 stages with relapsed or refractory non-Hodgkin’s lymphoma. Stage 1 of the study was designed to provide a preliminary assessment of monotherapy activity, with stage 2 designed to further evaluate safety and efficacy of daratumumab monotherapy. Stage 2 will now not proceed. The primary endpoint of the study was overall response rate. The safety profile of daratumumab in these diseases was also assessed.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, NK/T-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapiesa

Curis to Present Preclinical Data on IRAK4 Kinase Inhibitor CA-4948 at AACR Annual Meeting

On March 30, 2017 Curis, Inc. (Nasdaq:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, reported that Curis scientists will present data from its IRAK4 kinase inhibitor development candidate, CA-4948, at the Annual Meeting of American Association of Cancer Research (AACR) (Free AACR Whitepaper) to be held April 1 — 5, 2017 in Washington, D.C (Press release, Curis, MAR 30, 2017, View Source [SID1234518321]). Curis has exclusive license to CA-4948 under a collaboration agreement with Aurigene established in 2015.

Additional information follows. Abstracts can be accessed at www.aacr.org.

Poster Presentation
Date/Time: Monday, Apr. 3, 2017, 8:00 AM – 12:00 PM
Session Title: Novel Molecular Targets 1
Session Category: Experimental and Molecular Therapeutics
Presentation Title: Efficacy of the IRAK4 Inhibitor CA-4948 in Patient-Derived Xenograft Models of
Diffuse Large B Cell Lymphoma
Abstract Number: 1168