On March 6, 2017 OncoCyte Corporation (NYSE MKT:OCX), a developer of novel, non-invasive blood based tests to aid in the early detection of cancer, reported the successful completion of a critical step in the development of its lung cancer diagnostic test (Press release, BioTime, MAR 6, 2017, View Source [SID1234518005]).

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While the key performance metrics of its diagnostic cannot be revealed until they are presented at the American Thoracic Society Meeting in May, the company has locked its prediction algorithm and intends to move to the Clinical Validation Phase of development—the last phase before commercial launch. The data from the study exceed levels OncoCyte believes necessary for a commercially successful test and the Company is moving forward with plans to launch the lung cancer diagnostic test during the second half of 2017.

OncoCyte’s algorithm confirmed the results of an earlier study by The Wistar Institute of Anatomy and Biology, which reported its results at the CHEST 2016 Annual Meeting in October 2016. The Area Under the Curve (AUC) in Wistar’s study was 0.82 with a sensitivity of 90% and specificity of 62%. OncoCyte’s study results were consistent with Wistar’s.

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 nodules that are identified correctly by the test and specificity measuring the percentage of benign nodules correctly identified.

OncoCyte’s assessment of the market leads management to believe that it is positioned to be the first company to provide a highly accurate non-invasive confirmatory blood test for lung cancer. Based on published sources, Lung RADS guidelines and NLST (National Lung Screening Trial) data, the Company estimates that approximately 1.4 million patients annually in the U.S. could benefit from its test. Assuming this number of patients and the Company’s currently planned pricing for such a test, the total addressable market could potentially exceed $4 billion. OncoCyte believes that its blood based lung cancer test can provide Medicare and private insurance companies with significant savings if the price of its product is about 20 to 25 percent of the cost of an invasive lung biopsy, which according to recent Medicare estimates averages approximately $15,000. Potential revenue to OncoCyte will depend in large measure on the test’s market penetration and on approved reimbursement by Medicare and health insurers.

The results of OncoCyte’s study will be presented at The American Thoracic Society conference in May by its lead author, Dr. Anil Vachani, Associate Professor of Medicine at the Hospital of the University of Pennsylvania, located in Philadelphia, PA. "If the assay continues to perform at these levels, it could create a significant improvement in the standard of care in lung nodule management. Current practice can result in patients undergoing avoidable invasive procedures, which a diagnostic test of this type could help to reduce significantly, while also lowering the cost to determine the presence of lung cancer," said Dr. Vachani.

OncoCyte’s study utilized Wistar’s biomarker panel, which has been exclusively licensed to OncoCyte. The study developed and tested OncoCyte’s proprietary algorithm, using approximately 300 samples collected from patients at 26 community based, academic and government sites across the United States. OncoCyte developed its algorithm by combining data from the top mRNA biomarkers with clinical data such as nodule size. The algorithm was self-tested via a six-fold internal cross-validation on the samples. Cross-validation is a statistical method used to develop and estimate the performance of an algorithm.

The samples were collected from patients with nodules ranging in size from five to thirty millimeters, the size range presenting the greatest diagnostic challenge to clinicians. For patients with these size nodules, physicians must weigh the risk of cancer against the risks posed by costly and potentially dangerous invasive biopsies to confirm whether the nodules are malignant or benign.

Because of the study’s successful results, OncoCyte also announced that it will begin ramping-up its commercial capabilities in anticipation of the potential launch of the test. OncoCyte will initiate a Clinical Validation Phase for this diagnostic. During this phase, the company will continue to carry out analytical validation studies to refine its operational stage laboratory processes and will apply for certification of its CLIA diagnostic testing lab. Upon CLIA certification, OncoCyte will conduct a small CLIA lab validation study to demonstrate that the full assay system utilized in the CLIA lab provides the same results on clinical samples as those obtained in the R&D lab. OncoCyte then will begin a clinical validation study using the finalized algorithm and operational procedures on a new set of at least 300 blinded prospectively collected samples to confirm whether the sensitivity and specificity of the test remain within commercial parameters in a CLIA operational setting. Assuming successful completion of these steps, OncoCyte anticipates launching the test commercially in the second half of 2017.

"We are very excited about the successful results of our study," commented William Annett, President and Chief Executive Officer. "Our goal is to have the first commercial blood test that can help physicians to better manage patients presenting with lung nodules, and to avoid a significant number of risky and costly biopsies."

On March 6, 2017 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has indicated the Investigational New Drug (IND) application for ADXS-NEO, a personalized neoantigen-targeted approach to cancer immunotherapy that is being developed in collaboration with Amgen, can proceed (Press release, Advaxis, MAR 6, 2017, View Source [SID1234518004]).

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This ground-breaking IND paves the way for bringing a new precision immunotherapy for the treatment of cancers into the clinic this year. ADXS-NEO employs Advaxis’ proprietary Listeria monocytogenes (Lm)-based antigen delivery technology, its Lm Technology, to target multiple patient-specific neoantigens in each individual patient’s tumor that are not present in normal cells. ADXS-NEO is designed to stimulate both the innate and adaptive arms of the immune system.

Advaxis bioengineers ADXS-NEO constructs by programming its Lm-based antigen delivery technology to present the unique protein fragments or neoantigens associated with mutations found in a patient’s own cancer cells. These cancer-specific mutations are identified by comparing the DNA sequences of cancer cells with normal cells. ADXS-NEO works by presenting a large payload of neoantigens directly into dendritic cells within the patient’s immune system to generate new cancer-fighting white blood cells. These T cells hunt down cancer cells bearing these neoantigens while at the same time broadly stimulating the immune system and reducing the ability of the cancer to resist.

ADXS-NEO constructs can present multiple neoantigens that can be targeted by a patient’s immune system simultaneously. Tumors may accumulate up to 100 or more mutations that can generate neoantigens, and each patient has a set of mutations that are unique to his or her own tumors. ADXS-NEO is designed to hit multiple targets at once to improve the likelihood of a benefit.

ADXS-NEO will be manufactured in Advaxis’ newly constructed facility in Princeton, N.J., utilizing a process that minimizes the time required to develop the patient-specific immunotherapy. A single manufacturing run can provide sufficient product to treat each patient repeatedly for more than one year.

"The IND acceptance is a landmark step towards escaping the one-size-fits-all approach to cancer treatments by building innovative, patient-specific immunotherapies. This highly personalized approach has the potential to transform the treatment of care across multiple types of cancers," said Robert Petit, Ph.D., Chief Scientific Officer of Advaxis. "This enables us to employ Lm Technology to focus the attention of a patient’s immune system against the very mutations within their cancer that turned their cells malignant in the first place."

ADXS-NEO is under development through a collaboration between Amgen and Advaxis, bringing together Amgen’s expertise in immuno-oncology development and commercialization and Advaxis’ proprietary Lm-based antigen delivery technology and it’s My Immunotherapy Neo-Epitopes or MINE platform. Advaxis plans to initiate a phase 1 trial evaluating ADXS-NEO in multiple tumor types later this year.

"Over the past several years, the field of cancer immunotherapy has brought promising new treatments with meaningful benefits to cancer patients. Amgen remains committed to a multi-modality approach in immunotherapy, and our collaboration with Advaxis adds to the toolkit of cancer-fighting options available for patients," said David M. Reese, Senior Vice President, Translational Sciences at Amgen. "We look forward to our continued work with Advaxis to explore the potential of ADXS-NEO in the clinic and across multiple tumor types."

On March 6, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported data presentations relating to its technology platforms to be given at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in Washington, D.C., April 1 through April 5, 2017 (Press release, Aduro Biotech, MAR 6, 2017, View Source [SID1234518003]).

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Abstract 2645: Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma

Date/Time: Monday, April 3, 1:00 p.m. to 5:00 p.m. ET
Location: Convention Center, Halls A-C
Poster section 26; Board number 4

Abstract 2993: STING signaling in breast tumor microenvironment modulates immune checkpoint blockade efficacy in the neu-N mouse model of breast cancer

Date/Time: Monday, April 3, 3:05 p.m. to 3:20 p.m. ET
Location: Room 152, Level 1, Washington Convention Center
Session: Innate Immune Mechanisms in Cancer Treatment – Oral Presentation

Late-Breaking Research: Immunology

Abstract LB-198:

Combination of PEGylated recombinant hyaluronidase PH20 (PEGPH20) with live-attenuated, double-deleted (LADD) Listeria enhances tumor infiltrating CD8+ T cell response and antitumor efficacy in mice

Date/Time: Tuesday, April 4, 8:00 a.m. to 12:00 p.m. ET
Location: Convention Center, Halls A-C
Poster section 35; Board number 21

On March 6, 2017 TG Therapeutics (NASDAQ:TGTX) reported positive topline results from its Phase 3 GENUINE clinical trial of TG-1101 (ublituximab) plus ibrutinib in patients with previously treated high risk Chronic Lymphocytic Leukemia (CLL) (Press release, TG Therapeutics, MAR 6, 2017, View Source [SID1234518002]). For the study, high risk was defined as having any one or more of the following: 17p deletion, 11q deletion or p53 mutation.

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The multicenter, randomized trial (NCT02301156), which assessed the efficacy and safety of TG-1101 plus ibrutinib, met its primary endpoint, demonstrating a statistically significant improvement in Overall Response Rate (ORR) compared to ibrutinib alone in both the Intent to Treat (ITT) population (p=0.001) and Treated population (p < 0.001). The ITT population includes all 126 randomized patients (64 in the TG-1101 + ibrutinib arm and 62 in the ibrutinib alone arm) while the Treated population includes all ITT patients that received at least one dose of either study drug (59 in the TG-1101 + ibrutinib arm and 58 in the ibrutinib alone arm).

Overall Response Rates

TG-1101 plus Ibrutinib Ibrutinib P-value
Treated Population (n) n=59 n=58
Overall Response Rate 80 % 47 % P < 0.001
All responses were assessed by independent blinded central review using the iwCLL 2008 guidelines. Per iwCLL guidelines, responders require confirmation of response for a minimum duration of 2 months. As of the date of the analysis, each arm had responders that were awaiting confirmation visits which are scheduled to occur over the next two months. During the study it was infrequent (less than 3% in the combination arm) for initial responses to fail to be confirmed. Median follow-up for the study was approximately 12 months.

The GENUINE study was designed to demonstrate the value of adding TG-1101, a highly potent next generation glycoengineered anti-CD20 monoclonal antibody to ibrutinib monotherapy in high risk CLL, and was powered to show a statistically significant improvement in ORR, with a minimal absolute detectable difference between the two arms of approximately 20%. The absolute difference between the arms was approximately 30% resulting in a p-value of ≤ 0.001. Results from registration directed studies included in the ibrutinib prescribing information demonstrate single agent ibrutinib response rates ranging from 43% to 58% in patients with previously treated CLL, with the findings from the GENUINE study of 47% ORR for ibrutinib fitting well within historical experience.

In addition to ORR, observed advantages were seen for the combination in a number of secondary and other efficacy measures, including radiographic Complete Response (CR) rate, Progression Free Survival and Time to Response. Sufficient data on MRD negative status and bone marrow confirmation of radiographic CRs were not available at the time of analysis. From a safety standpoint, the combination was well tolerated with a safety profile consistent with the Phase 2 study of ublituximab plus ibrutinib recently published in the British Journal of Haematology.

A full analysis of the Phase 3 GENUINE data along with detailed efficacy and safety results will be submitted for presentation at a medical meeting in the first half of 2017 and the Company plans to meet with the FDA as soon as possible thereafter to discuss the filing of the data for accelerated approval.

"TG-1101 is a highly potent next generation glycoengineered anti-CD20 monoclonal antibody. We believe the data today demonstrate that the addition of TG-1101 to ibrutinib enhances the therapeutic benefit of ibrutinib in patients with previously treated high risk CLL, the patient population with the poorest outcome on ibrutinib. We believe the results observed in the combination arm are extremely compelling and the regimen has the potential to become the standard of care for treating patients with high risk CLL that have progressed from other therapies," said Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics. Mr. Weiss continued, "We believe that using combination therapy to accelerate and deepen response in poor prognosis high risk CLL is critically important for patient outcomes and we look forward to sharing these data with the FDA in the coming months to discuss filing for accelerated approval. Most importantly, we would like to thank the investigators and their patients for participating in this significant research."

Dr. Jeffrey Sharman, the GENUINE Phase 3 Study Chair and the Medical Director for Hematology Research for the US Oncology Network, commenting on the results stated, "Ibrutinib has been a great addition to our CLL armamentarium, however we have long believed that ibrutinib alone may not be enough, particularly for patients with high-risk disease. This study demonstrates that the addition of ublituximab, can significantly enhance the response rates without compromising safety. We believe that the rapid responses seen in our Phase 2 study with ublituximab plus ibrutinib are validated here in our Phase 3 GENUINE study and are important markers of improved overall efficacy and patient outcomes. I look forward to the presentation of the results at an upcoming medical meeting."

ABOUT THE PHASE 3 GENUINE STUDY

The Phase 3 GENUINE study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of TG-1101 (ublituximab) plus ibrutinib compared to ibrutinib alone in adult patients with high risk Chronic Lymphocytic Leukemia (CLL) who received at least one prior therapy for their disease.

The study was conducted at 160 clinical trial sites in the US and Israel and randomized 126 patients. Patients received ibrutinib orally at 420 mg once daily in both arms and in the treatment arm those patients also received intravenous infusions of TG-1101 at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the treatment arm who had not progressed received quarterly infusions of TG-1101 maintenance at 900 mg.

On March 6, 2017 Exelixis, Inc. (Nasdaq: EXEL) reported that the U.S. Food & Drug Administration (FDA) has granted orphan drug designation to cabozantinib for the treatment of hepatocellular carcinoma (HCC) (Press release, Exelixis, MAR 6, 2017, View Source [SID1234518001]). This information was posted to FDA’s website on March 4, 2017 and can be accessed at

View Source

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A pivotal phase 3 trial (CELESTIAL) of cabozantinib is ongoing in patients with advanced HCC, and Exelixis has guided that data from the trial are expected in 2017.

Orphan drug status is granted to treatments for diseases that affect fewer than 200,000 people in the U.S. and provides certain incentives for medications intended for the treatment, diagnosis or prevention of rare diseases. At present, these incentives include seven years of marketing exclusivity for the orphan indication, certain federal grants, tax credits and waiver of certain FDA fees.

About the CELESTIAL Trial

CELESTIAL is designed to enroll 760 patients with advanced HCC who received prior sorafenib. Patients are randomized 2:1 to receive 60 mg of cabozantinib daily or placebo. The primary endpoint for the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety. The CELESTIAL trial is being conducted at more than 100 sites globally in 19 countries.