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.