On September 11, 2017 OncoCyte Corporation (NYSE American:OCX), a developer of novel, non-invasive liquid biopsy tests for the early detection of cancer, reported that data from its most recent breast cancer diagnostic study has been selected for presentation in a poster session at the 2017 San Antonio Breast Cancer Symposium (SABCS) (Press release, BioTime, SEP 11, 2017, View Source [SID1234520468]). The SABCS will take place at the Henry B. Gonzalez Convention Center in San Antonio, Texas, from December 5-9, 2017.

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The data to be presented are from the Company’s NICE-BC (Non-Invasive Confirmatory dEtection (of) Breast Cancer follow-on study. The data confirm the findings from OncoCyte’s previous breast cancer study, which were presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2016. In the earlier study, the 15-marker model resulted in an area under the curve (AUC) of 0.92 with a sensitivity of 90% and specificity of 76%. Given this level of accuracy, and subject to successful completion of further R&D and clinical studies, OncoCyte’s novel panel of serum protein biomarkers may become the foundation of a highly accurate, non-invasive breast cancer diagnostic test.

The AUC of a test is a measure that combines sensitivity and specificity to express its total accuracy, with 1.0 being perfect accuracy and 0.50 being a random result. Sensitivity and specificity are statistical measures of test performance, with sensitivity measuring the percentage of malignant lumps or masses that are identified correctly by the test and specificity measuring the percentage of benign lumps or masses correctly identified.

"The presentation of data from our ongoing breast cancer diagnostic studies is another important step in the development of our non-invasive breast cancer diagnostic test," said William Annett, President and Chief Executive Officer. "There is a significant unmet need for a confirmatory breast cancer test that would reduce the number of unnecessary invasive biopsies and lower the financial burden to the healthcare system. We look forward to continued development of this important program."

The data from the NICE-BC study will be presented at SABCS 2017 by Philip McQuary, Ph.D., Director of Product Development at OncoCyte.

Abstract Title: Assessment of an immune response panel of serum protein biomarkers for the non-invasive detection of breast cancer
Poster Session: 4
Session Title: Detection/Diagnosis: Circulating Markers
Session Date: December 7, 2017
Session Time: 7:00 am CT – 9:00 am CT

The current standard of care for breast cancer diagnosis – annual or biannual mammogram screenings – does not meet the needs of large populations of women for whom mammography alone is not sufficient. These populations include women with dense breast tissue, genetic mutations (BRCA), a family history of breast cancer, or those who have suspicious mammogram screening results (BIRADs 3 or 4). The Company’s non-invasive liquid biopsy breast cancer diagnostic is intended to be a confirmatory, post-mammogram test that would address the needs of some of these populations, thereby reducing the number of patients subjected to invasive procedures.

According to published reports, there are about 39 million mammograms performed annually in the U.S., resulting in 1.6 million breast biopsies per year. Of these, only 260,000 (16%) result in a cancer diagnosis. The large number of suspicious findings in diagnostic mammograms leads to a significant amount of unnecessary invasive follow-up procedures. The financial burden to the healthcare system imposed by the follow-up testing of false-positive mammograms and breast cancer over-diagnosis is estimated to be $4 billion a year.

About Breast Cancer

Breast cancer is the second most common cancer among US women. Current screening guidelines set forth by the American Cancer Society recommend screening mammography for the early detection of breast cancer in women at average risk. Specifically, guidelines call for annual mammography for asymptomatic women age 45 to 54 and once every two years for women age 55 and older. Suspicious screening mammograms are generally followed up with a diagnostic mammogram and sometimes by an MRI (Magnetic Resonance Image) or an ultrasound. Ultimately, suspicious findings unresolved by imaging typically result in the recommendation of a breast biopsy.

On September 11, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO), reported that an interim data analysis showed that its INO-5150 cancer immunotherapy product generated antigen-specific CD8+ killer T cell responses measured in peripheral blood from subjects with biochemically recurrent prostate cancer (Press release, Inovio, SEP 11, 2017, View Source;In-Patients-with-Recurrent-Prostate-Cancer/default.aspx [SID1234520467]). The immunology results demonstrate that INO-5150 treatment as a monotherapy generated prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA) specific T cell responses in peripheral blood in 60% (35/58) of the subjects. Moreover, patients with specific CD8+ T cell responses experienced dampening in the rise of PSA and significant increases in PSA Doubling Times (PSADT). PSA is a prostate cancer associated biomarker and positive changes on PSA levels could signal INO-5150’s potential positive impact on the treatment of prostate cancer.

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These results were presented as a poster discussion on September 10th at the 2017 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting in Madrid, Spain.

Dr. Neil Shore, MD, Medical Oncologist at Urologic Associates of North Carolina, and the principal investigator of this study said, "Immunotherapy is an exciting new approach being evaluated for the treatment of many cancers including prostate cancer, where a small subset of patients have been shown to demonstrate clinical benefit from such therapy in the form of checkpoint inhibitors. Our study provides encouraging immunologic and clinical data that Inovio’s immunotherapy product can generate antigen-specific CD8+ killer T cell responses in the blood and link such responses to PSA changes in prostate cancer patients. Our results suggest that further evaluation of this product in prostate cancer patients should be explored."

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "As a leader in active immunotherapy for cancer with its lead program in phase 3, Inovio is pleased to report on promising phase 1b clinical trial data of our prostate cancer therapy INO-5150. The immunotherapy’s ability to generate anti-prostate cancer CD8+ T cell responses in patients dosed is truly exciting. Perhaps even more importantly, we also observed that the treated patients with better T cell responses saw a slower rise of PSA levels compared to those without the T cell responses.

We believe the new clinical data positions INO-5150 as an attractive T cell generating immunotherapy component of a potential combination regimen. In this regard, Inovio already has one the most extensive and dynamic T cell immunotherapy combo portfolio in our field, with three different PD-1/PDL-1 immuno-oncology combo efficacy studies with 3 different collaborators – MedImmune, Regeneron, and Genentech for MEDI0457 and INO-5401."

INO-5150, an active immunotherapy targeting both PSA and PSMA antigens which are present in the majority of prostate cancer cells, is administered with and without INO-9012, Inovio’s DNA-based IL-12 immune activator. INO-5150 is designed to activate patients’ immune responses and to specifically target prostate cancers expressing PSA and PSMA. This open label phase 1b study has fully enrolled 62 subjects with biochemically recurrent (rising PSA) prostate cancer and is intended to assess the safety, tolerability, dosing and immunogenicity of INO-5150 alone or in combination with INO-9012. This multi-centered study is also evaluating changes in PSA levels and kinetics, as PSA is an important biomarker in prostate cancer.

INO-5150 was generated using Inovio’s proprietary technology 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. PSMA is also one of 3 antigens comprising INO-5401, which is being tested as an immunotherapy to treat glioblastoma multiforme and metastatic bladder cancer in combination with Regeneron and Genentech’s checkpoint inhibitors, respectively.

This poster presentation provided immune response and clinical correlation across all four cohorts. In addition to immune responses, clinical correlative analyses evaluating PSA kinetics showed that patients with specific CD8+ T cell responses experienced dampening in the rise of PSA and significant increases in PSADT. Additional prostate cancer tissue analyses are ongoing to further investigate immunological correlation.

About Prostate Cancer and Biochemically Recurrent Prostate Cancer (BRPC)

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. There are about 60,000 patients each year in the US that develop biochemically recurrent prostate cancer (BRPC). The development of a new treatment for prostate cancer would be a significant medical advance given that current standard-of-care treatment options (surgery, radiation and hormone deprivation), while somewhat effective, all carry deleterious side effects and are often not a long-term cure.

On September 11, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that new preclinical data for its first-in-class clinical stage antibodies IPH5401 and monalizumab, were presented at the 3rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy conference, September 6 – 9, 2017, in Frankfurt, Germany (Press release, Innate Pharma, SEP 11, 2017, View Source [SID1234520466]).

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Poster #B184 shows the selective expression of C5aR on myeloid-derived suppressor cells (MDSC) and neutrophils. These cells accumulate within the tumor microenvironment and secrete pro-angiogenic factors which promote tumor progression. They also inhibit NK and T cells and suppress anti-tumor immunity.

In this poster, the data demonstrate that IPH5401 selectively inhibits the activation of neutrophils. Moreover, the data show that the combined administration of anti-C5aR with anti-PD-1 reduced tumor growth. Taken together, these data suggest that C5aR blockade may result in a more permissive environment for immune-mediated tumor killing and treatment with checkpoint inhibitors.

Poster #A130 demonstrates that blocking both NKG2A/HLA-E and PD-1/PD-L1 pathways enhance anti-tumor efficacy of CD8+ T cells. The data show that the deletion of either NKG2A (Qa-1b) or PD-L1 significantly delays tumor growth, suggesting that both receptors are involved in the immune-escape of tumors. Combined PD-L1 and NKG2A blockade achieved a complete response of 82%, compared to 54% for anti-PD-L1 and 36% for anti-NKG2A alone. CD8+ tumor infiltrated lymphocytes (TILs) expressing high levels of PD-1 co-expressed high levels of NKG2A, raising the possibility that NKG2A blockade may potentiate PD-1/PD-L1 blockers by directly enhancing CD8+ T cell-mediated killing of tumors.

Yannis Morel, Executive Vice President Products Portfolio Strategy of Innate Pharma, said: "We are encouraged by the preclinical data for IPH5401, which further support the development of this first-in-class anti-C5aR antibody especially in combination with PD‑1/PD‑L1 checkpoint inhibitors. We look forward to start clinical trials in oncology with IPH5401 in 2018.

In addition, preclinical data indicate that NKG2A blockade in conjunction with PD-L1 blockade enhances anti-tumor efficacy of CD8+ T cells and provide further evidence to support the ongoing clinical trial evaluating monalizumab, Innate’s first-in-class NKG2A checkpoint inhibitor, in combination with durvalumab, AstraZeneca/Medimmune’s PD-L1 checkpoint inhibitor."

Poster #B184 and Poster A#130 are available on Innate Pharma’s website.

On September 11, 2017 Ignyta, Inc. (Nasdaq:RXDX), a biotechnology company focused on precision medicine in oncology, provided an update on entrectinib—an orally bioavailable, CNS-active tyrosine kinase inhibitor being developed in tumors that harbor NTRK fusions or ROS1 fusions, currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2—and RXDX-105—an investigational, VEGFR-sparing, potent RET inhibitor (Press release, Ignyta, SEP 11, 2017, View Source [SID1234520465]).

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"Building on last week’s announcement of the completion of enrollment of the entrectinib efficacy data set for NDA submission in ROS1 fusion-positive non-small cell lung cancer, we are equally excited to also have completed enrollment of the efficacy data set for NDA submission in the NTRK tissue-agnostic indication," said Jonathan Lim, M.D., chairman and CEO of Ignyta. "We look forward to dual registration submissions in 2018 for these two independent, high unmet need, molecularly defined populations."

Entrectinib program updates:

Based on written feedback from the FDA, Ignyta confirms completion of enrollment of the efficacy data sets for both the NTRK tissue-agnostic (i.e., fusion-positive solid tumor) cohort and the ROS1 NSCLC cohort to support dual NDA submissions in 2018.
No additional studies were requested for these submissions.
Entrectinib was intentionally designed to cross the blood-brain barrier and has demonstrated CNS activity. Specific guidance was provided by FDA on inclusion of entrectinib CNS efficacy data in future prescribing information for both NTRK and ROS1.
An update on data from STARTRK-2 on entrectinib in ROS1 NSCLC, including an additional six months of follow-up, will be presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan October 18, 2017. Previous interim data were shared in an investor update call in April 2017.
Additionally, a recent joint meeting with the Center for Devices and Radiological Health (CDRH) and the Center for Drug Evaluation Research (CDER) on companion diagnostic strategy for entrectinib confirms the premarket approval submission plan and timeline for Trailblaze Pharos are tracking with the dual NDA submissions in NTRK and ROS1.
RXDX-105 program updates:

New Phase 1b clinical data on RXDX-105 presented this week at the ESMO (Free ESMO Whitepaper) 2017 Congress in Madrid, Spain demonstrated clinical activity in RET fusions and compelling response rate in an ultra-rare lung cancer population.

Safety –

A total of 152 patients, with a range of solid tumors, have been treated in the Phase 1/1b clinical trial, including 74 patients treated at the recommended Phase 2 dose of 275mg daily in the fed state, and 43 patients treated at a dose of 350mg daily in the fed state.
RXDX-105 continues to be well tolerated, with the most common treatment-related adverse events Grade 1 or 2 and reversible with dose modifications. The most common Grade 3 treatment-related adverse events ( > 5 percent) were rash (10 percent), hypophosphatemia (7 percent) and elevated ALT (7 percent).
Importantly, toxicities commonly associated with VEGFR inhibition, such as hypertension, hypothyroidism, proteinuria and neurotoxicity were rarely observed ( < 5 percent); and RXDX-105 was not associated with Qt/QTc prolongation.
Efficacy –

Of those treated, 22 patients had NSCLC harboring RET fusions and were RET inhibitor naïve, making them evaluable for response.
A preliminary objective response rate of 75 percent was observed in patients with non-KIF5B-RET fusions, with six of eight patients achieving a confirmed partial response. In contrast, those with KIF5B-RET fusions (14 patients) did not demonstrate a RECIST response. These data are consistent with previous studies that suggest that KIF5B-RET fusions may be less susceptible to RET inhibition.
The longest duration of response (DOR) in a responding patient with non-KIF5B-RET fusion was 10.2 months and ongoing; two-thirds of responding patients currently continue on treatment in active response; median DOR therefore has not yet been reached.
Development plan –

This robust clinical trial design has employed next generation sequencing to identify the precise patient populations most likely to benefit from RXDX-105 – those with non-KIF5B-RET fusions – which is estimated to be approximately 800 new patients per year in the United States.
The RXDX-105 Phase 1b study will be concluded with no further enrollment. Those currently receiving treatment will remain on study.
Ignyta will continue discussing RXDX-105 with potential partners and will provide an update on this program in the first half of 2018.

On September 11, 2017 DelMar Pharmaceuticals (Nasdaq: DMPI) ("DelMar" and "the Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported the initiation of a Phase 2 clinical trial for its lead agent VAL-083 in newly diagnosed MGMT-unmethylated glioblastoma multiforme (GBM) (Press release, DelMar Pharmaceuticals, SEP 11, 2017, View Source [SID1234520461]). The biomarker-driven clinical trial will explore safety and efficacy of chemoradiation with VAL-083 as an alternative to standard-of-care temozolomide in patients with MGMT-unmethylated GBM.

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"This small trial has the ability to pave the way for a significant treatment paradigm change for patients with newly diagnosed GBM. Positive data from this study will serve as a lead-in to a randomized global trial and set the stage for VAL-083 to potentially become the standard of care for approximately two-thirds of newly diagnosed GBM patients," commented Jeffrey Bacha, Chief Executive Officer of DelMar Pharmaceuticals.

The trial, which is being funded under the terms of DelMar’s collaboration with Guangxi Wuzhou Pharmaceutical Group Co. Ltd. (Guangxi Wuzhou Pharma), is being conducted at Sun Yat-sen University Cancer Center (SYUCC) in Guangzhou, China under the direction of Prof. Zhong-ping Chen, M.D., Ph.D. Prof. Chen is the Chair of the Department of NeuroSurgery/Neuro-Oncology at SYUCC and a member of the editorial board of the Journal of NeuroOncology.

The study will enroll 20-30 newly diagnosed GBM patients whose tumors exhibit high-expression of the DNA-repair enzyme O6-methylguanine methyltransferase (MGMT) and will be treated with VAL-083 in combination with radiotherapy to examine the safety and efficacy of VAL-083 in this population. MGMT methylation status will be used as a biomarker for patient selection and only patients whose tumors are MGMT-unmethylated will be enrolled.

GBM patients with MGMT-unmethylated tumors exhibit a high expression of the MGMT enzyme. MGMT expression is correlated with resistance to temozolomide, the current front-line chemotherapy used in the treatment of GBM. MGMT-unmethylated patients have particularly poor patient outcomes and significantly reduced survival compared to MGMT-methylated patients. VAL-083 has demonstrated anti-cancer activity independent of MGMT expression against multiple GBM cell lines in vitro.

The primary efficacy endpoint of this trial is progression free survival (PFS). Based on enrollment projections, it is expected that safety/tolerability and primary efficacy (PFS) data from this trial will become available within 9 months and 15 months, respectively from start of enrollment. Results will be used to guide the design of global randomized studies, which if successful, will position VAL-083 as a potential replacement for the current standard-of-care (chemoradiation with temozolomide) in newly diagnosed GBM patients, particularly for the approximately 2/3 of patients whose tumors feature MGMT-unmethylated GBM. Further details of the trial can be found at clinicaltrials.gov (Identifier Number: NCT03050736)

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM in historical clinical trials sponsored by the U.S. National Cancer Institutes (NCI).

VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas.

DelMar has demonstrated that VAL-083’s anti-tumor activity against GBM is unaffected by the expression of MGMT in vitro. Further details regarding these studies can be found at View Source

The Company’s recent outcomes in Phase 1-2 clinical trials suggested that VAL-083 may offer a clinically meaningful survival benefit for patients with recurrent GBM following treatment with both TMZ and bevacizumab. A well-tolerated dosing regimen of 40mg/m2/day on days 1, 2, and 3 of a 21-day cycle was selected for study in subsequent GBM clinical trials.

Overall VAL-083’s clinical activity as a potential treatment for GBM has been established by DelMar’s recent clinical trials in refractory GBM and historical trials conducted by the NCI. In prior NCI trials, VAL-083 combined with radiotherapy in newly diagnosed GBM (all MGMT status) demonstrated superior benefit versus radiotherapy alone (8.3 months) in comparison to similar studies involving temozolomide or nitrosoureas (1.2 – 2.5 months).

Based on these results, DelMar has embarked on human clinical trials for VAL-083 across multiple lines of GBM therapy. These trials include, i) an ongoing single-arm, biomarker driven, Phase 2 study to determine if VAL-083 treatment of MGMT-unmethylated adult GBM patients at first recurrence/progression, prior to bevacizumab, improves overall survival, compared to historical control with lomustine (clinicaltrials.gov identifier: NCT02717962); ii) a pivotal, randomized Phase 3 study in temozolomide-Avastin Recurrent GBM ("STAR-3") to evaluate overall survival versus salvage chemotherapy (clinicaltrials.gov identifier: NCT03149575); iii) a single arm, biomarker driven, Phase 2 study to confirm the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels (clinicaltrials.gov identifier: NCT03050736). The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM.

About Glioblastoma Multiforme (GBM)

Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain cancer. Approximately 18,000 patients are diagnosed with GBM in the United States and 25,000 in Europe each year. Current standard of care includes surgery, radiation and treatment with temozolomide (TMZ), however nearly all tumors recur and the prognosis for recurrent GBM is dismal. Approximately two-thirds of newly diagnosed GBM patients have tumors characterized by an unmethylated promoter for O6-methylguanine methyltransferase (MGMT); a validated biomarker for TMZ-resistance. Second-line treatment with anti-angiogenic agent bevacizumab has not improved overall survival (OS) and 5-year survival is less than 3%.