On July 27, 2015 The University of Colorado Cancer Center and Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company focused on the discovery, development and commercialization of targeted cancer therapies, reported the publication of a research brief in the online edition of the journal Cancer Discovery, describing the first patient with a tropomyosin receptor kinase (TRK) fusion cancer enrolled in the Phase 1 dose escalation trial of LOXO-101, the only selective TRK inhibitor in clinical development (Press release, Loxo Oncology, JUL 27, 2015, View Source [SID:1234506711]).

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Additional contributors to the paper include the Knight Cancer Institute at Oregon Health & Science University and Foundation Medicine, Inc. (Nasdaq:FMI).

The peer-reviewed research brief describes a female patient with advanced soft tissue sarcoma widely metastatic to the lungs. The patient’s physician submitted a tumor specimen to Foundation Medicine for comprehensive genomic profiling with FoundationOne Heme, where her cancer was demonstrated to harbor a TRK gene fusion. Following multiple unsuccessful courses of treatment, the patient was referred to the University of Colorado for enrollment in the Phase 1 trial of LOXO-101 in March 2015. On study, the patient’s shortness of breath rapidly resolved and she was able to discontinue her supplemental oxygen and resume activities of daily living. Imaging studies following one month of treatment, the first imaging studies conducted post-treatment, confirmed that her tumors had substantially regressed, meeting a partial response (PR) definition by standard RECIST 1.1 criteria. As discussed in the publication, with four months of treatment, additional CT scans demonstrated almost complete tumor disappearance of the largest tumors. After four months of dosing, the patient did not have any adverse events that were attributed to LOXO-101.

"It is exciting to think that TRK fusions may join a relatively short, but growing, list of actionable oncogenic drivers found across human cancer," said lead author Robert C. Doebele, M.D., Ph.D., LOXO-101 clinical investigator, and University of Colorado Cancer Center member. "To see a rapid and unequivocal response in the first TRK fusion patient treated with LOXO-101 provides early but encouraging validation of this target. Of course, it will be important to see repeatable and durable results as more patients with TRK fusions are treated over time. This case study also illustrates the clinical value of multiplex genetic testing in patients with advanced cancer. Broad testing for all known actionable molecular alterations gives patients the best opportunity to find commercially available or investigational targeted therapies that have been rationally designed to treat their cancers."

The publication also describes novel assays for assessing LOXO-101’s impact on TRK signaling, patient-derived TRK fusion models in vitro and in vivo which illustrate LOXO-101’s TRK inhibition, and the first-ever description of the molecular epidemiology of TRK fusions in soft tissue sarcoma.

LOXO-101, built specifically to inhibit TRK, is currently being studied in a Phase 1 trial of patients with advanced solid tumors. The trial continues to enroll patients at escalating oral doses of fixed once-daily and twice-daily regimens. As reported at the 2015 American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting, LOXO-101 has been well tolerated with no drug-related adverse event signals reported at doses that consistently achieve systemic drug exposures anticipated to inhibit TRK signaling by over 90%. For more information on the Phase 1 trial, including study sites and eligibility criteria, visit clinicaltrials.gov (study identifier NCT02122913), or contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123. Loxo Oncology’s Policy for Access to Investigational Agents can be found on the Loxo Oncology web site.

"TRK is increasingly recognized for its role in cancer biology, and this first peer-reviewed clinical validation is an important step forward," said Jennifer Low, M.D., Ph.D., chief medical officer of Loxo Oncology. "We continue to be encouraged by the safety and pharmacokinetics we have seen so far in the LOXO-101 Phase 1 trial, and we look forward to sharing more information about our clinical program later this year."

"Our goal is to better understand the genetic drivers of sarcoma to improve treatment options for patients," said Lara E. Davis, M.D., a medical oncologist and sarcoma specialist with the OHSU Knight Cancer Institute. "These early results validate that further study of TRK in the complex field of sarcoma is warranted."

The research presented in the publication is funded by a V Foundation Scholar Award and a Loxo Oncology research grant awarded to Dr. Robert C. Doebele. Also, the State of Colorado and University of Colorado Technology Transfer Office Bioscience Discovery Evaluation Grant Program, the University of Colorado Lung Cancer SPORE (funded by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) grant P50CA058187 provided funding to Dr. Doebele and the NIH/NCI CCSG P30CA046934 (Molecular Pathology Shared Resource) provided funding to Drs. Varella-Garcia and Aisner.

About LOXO-101

LOXO-101 is a potent, oral, selective inhibitor of tropomyosin receptor kinase (TRK) signaling molecules. The TRK family (TRKA, TRKB, and TRKC) has been implicated in diverse tumor types such as lung cancer, head and neck cancer, melanoma, colorectal cancer, sarcoma, and breast cancer. LOXO-101 was built specifically to inhibit TRK and is currently the only selective TRK inhibitor in clinical development. LOXO-101 is currently being evaluated in a Phase 1 dose escalation trial for patients with advanced solid tumors.

On July 27, 2015 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that it has initiated a phase I trial to evaluate Inovio’s DNA immunotherapy in men with biochemically relapsed prostate cancer (Press release, Inovio, JUL 27, 2015, View Source [SID:1234506708]).

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The launch of this human trial follows strong pre-clinical results revealing that INO-5150 generated robust CD8+ T cell responses in animal studies including non-human primates. The immune responses generated by INO-5150 were similar in character to immune responses generated by VGX-3100, Inovio’s immunotherapy for human papillomavirus (HPV) that regressed pre-cancerous cervical lesions and eliminated HPV in a randomized, placebo-controlled phase II trial.

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INO-5150 is a novel SynCon immunotherapy for prostate cancer targeting two antigens, prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA), present in the majority of prostate cancer cells. This phase I study will evaluate the safety, tolerability, and immunogenicity of INO-5150 alone or in combination with INO-9012, Inovio’s DNA-based IL-12 immune activator. The multi-centered study will also evaluate changes in PSA levels, an important biomarker in prostate cancer.

INO-5150 was generated using Inovio’s proprietary SynCon process to enable significant production of PSA and PSMA antigens with genetic sequences differentiated from native human PSA and PSMA sequences. This patented approach is designed to help the body’s immune system overcome its "self-tolerance" to prostate cancer cells and mount a strong targeted CD8+ killer T cell response to eliminate the cancerous cells displaying these antigens.

Dr. J. Joseph Kim, President and CEO, said, "Inovio is focused on taking immunotherapy to the next level. Inovio is the only immunotherapy company that is generating T cells, in vivo, in high quantity that are fully functional whose killing capacity correlates with relevant clinical outcomes. With positive results from our phase II study of VGX-3100, Inovio’s active immunotherapy technology is a promising approach to treat various solid tumors by targeting the most important antigens for a particular tumor. Today’s launch of our SynCon prostate cancer immunotherapy builds on Inovio’s current trials for several difficult-to-treat cancers including head and neck, cervical, breast, lung, and pancreatic cancer."

About Prostate Cancer

Prostate cancer is the second most frequently diagnosed cancer in men. Nearly three-quarters of the registered cases occur in developed countries. Accounting for nearly 300,000 deaths each year, prostate cancer is the sixth leading cause of death from cancer in men. The development of a new treatment for prostate cancer would be a significant medical advance given that present treatment options (surgery, radiation and hormone deprivation), while somewhat effective, all carry deleterious side effects and are often not a long-term cure.

On July 27, 2015 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted an accelerated assessment to ixazomib, an investigational oral proteasome inhibitor for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Takeda, JUL 27, 2015, View Source [SID:1234506702]).

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The EMA awards an accelerated assessment to those medicines deemed to be of major public health interest and, in particular, therapeutic innovation.

Takeda expects to submit a marketing authorisation application for ixazomib in the European Union (EU) in the coming weeks. The submission is based on the results of the first pre-specified interim analysis of the pivotal Phase 3 trial TOURMALINE-MM1. This study is an international, randomized, double-blind, placebo controlled clinical trial of 722 patients designed to evaluate the superiority of ixazomib plus lenalidomide and dexamethasone over placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Patients continue to be treated to progression in this trial and evaluated for long-term outcomes.

"We are pleased that the CHMP has granted accelerated assessment for ixazomib, and believe that this designation underscores the urgent need for therapeutic innovation in multiple myeloma treatments," said Andrew Plump, M.D., Ph.D., Takeda’s Chief Medical and Scientific Officer. "We look forward to sharing the TOURMALINE-MM1 study data from the first pre-specified interim analysis at an upcoming medical meeting, and greatly appreciate the ongoing dedication and commitment from the patients and their families who have been participating in the ixazomib clinical development program."

"Continuous therapy is emerging as a standard of care in multiple myeloma because it has demonstrated improved long-term outcomes," said Philippe Moreau, MD, University Hospital of Nantes in France. "If ixazomib is approved, for the first time physicians will have the option of an all-oral proteasome inhibitor-based regimen for the treatment of multiple myeloma, which could be a real advantage in delivering sustained therapy."

About Multiple Myeloma
Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of plasma cells, or myeloma cells, becomes cancerous and multiplies, increasing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer with approximately 39,000 new cases in the EU and 114,000 new cases globally per year.

About Ixazomib
Ixazomib (MLN9708) is an investigational oral proteasome inhibitor which is being studied in multiple myeloma, systemic light-chain (AL) amyloidosis, and other malignancies. Ixazomib was granted orphan drug designation in multiple myeloma in both the United States and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. Food and Drug Administration (FDA) for relapsed or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.

Ixazomib’s clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase 3 trials are ongoing:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma

TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)

TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT

TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis

For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.

On July 27, 2015 Bristol-Myers Squibb Company (NYSE:BMY) and AbbVie (NYSE:ABBV) reported the European Medicines Agency (EMA) validated for review the Marketing Authorization Application (MAA) for Empliciti, an investigational Signaling Lymphocyte Activation Molecule (SLAMF7)-directed immunostimulatory antibody, for the treatment of multiple myeloma as combination therapy in adult patients who have received one or more prior therapies (Press release, Bristol-Myers Squibb, JUL 27, 2015, View Source [SID:1234506698]).

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The application was granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities. Bristol-Myers Squibb has proposed the name Empliciti which, if approved by health authorities, will serve as the trade name for elotuzumab.

"The MAA validation marks a significant milestone in Bristol-Myers Squibb’s mission to advance the science and impact the treatment of hematologic malignancies through our Immuno-Oncology leadership," said Michael Giordano, MD, senior vice president, head of Oncology Development, Bristol-Myers Squibb. "We believe the CHMP’s acceptance for an accelerated assessment reflects the need for a new treatment option for multiple myeloma, a largely incurable disease. We are proud to be one step closer to bringing Empliciti to patients with relapsed or refractory multiple myeloma in Europe."

The MAA is primarily supported by data from two randomized clinical trials, each combining Empliciti with a different standard of care regimen for multiple myeloma. ELOQUENT-2, a Phase 3, randomized, open-label study, evaluated Empliciti in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone. The results of this trial were published in The New England Journal of Medicine on June 2. Additionally, a Phase 2, randomized, open-label study (Study CA004-009) evaluated Empliciti with bortezomib and dexamethasone versus bortezomib and dexamethasone alone. These Phase 2 results were presented in an oral session (Abstract #S103) at the 20th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

Empliciti previously obtained orphan drug designation in the European Union (EU). An orphan medicinal product must be intended for the treatment, prevention or diagnosis of a disease that is life threatening and chronically debilitating; the prevalence in the EU must not be more than five in 10,000. The medicine must be of significant benefit to those affected by the condition. If maintained, orphan drug designation allows sponsors to access a number of incentives including protocol assistance and receive market exclusivity for a ten-year period following approval.

About Empliciti

Empliciti is an investigational immunostimulatory antibody targeted against SLAMF7, a cell-surface glycoprotein that is highly and uniformly expressed on myeloma cells and Natural Killer (NK) cells, but is not detected on normal solid tissues or on hematopoietic stem cells. The safety and efficacy of Empliciti have not been evaluated by the FDA or any other health authority.

About Multiple Myeloma

Multiple myeloma is a hematologic, or blood, cancer that develops in the bone marrow. It occurs when a plasma cell, a type of cell in the soft center of bone marrow, becomes cancerous and multiplies uncontrollably. Despite advances in multiple myeloma treatment over the last decade, only 45% of patients have a ten-year survival rate. A common characteristic for many patients is that they experience a cycle of remission and relapse, in which they stop treatment for a short time, but eventually return to a treatment shortly after. Following relapse, less than 20% of patients are alive after five years. It is estimated that annually more than 114,200 new cases of multiple myeloma are diagnosed globally and annually more than 79,000 people die from the disease globally.