On March 25, 2019 Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II Variant Application to the European Medicines Agency (EMA) for DARZALEX ▼ (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of newly diagnosed patients with multiple myeloma who are not eligible for autologous stem cell transplantation (GATS) (Press release, Johnson & Johnson, MAR 25, 2019, View Source [SID1234534607]).

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"Today’s submission brings us a little closer to our goal of improving treatment outcomes for people newly diagnosed with multiple myeloma," said José Antonio Burón Vidal, vice president of medical affairs, Europe, Middle East and Africa (EMEA) region, Janssen-Cilag Limited. "We are extremely grateful to the patients and researchers who have participated in the MAIA clinical trial program and look forward to working closely with regulatory authorities to gain approval for this new association."

The application is supported by data from the MAIA Phase 3 Study (MMY3008), which was presented at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). 1 The study showed that at a median follow-up of 28 months, daratumumab-Rd significantly reduced the risk of disease progression or death by 44 percent in patients with newly diagnosed multiple myeloma who were not not eligible for transplant compared to treatment with Rd alone (risk ratio [HR] = 0.56, 95% confidence interval [CI]: 0.43-0.73, p <0.0001). 1Median progression-free survival with daratumumab-Rd has not yet been reached, compared to 31.9 months for patients who received Rd alone. 1 The addition of daratumumab resulted in more pronounced responses compared to Rd alone, including increased rates of complete response (CR) or better (48% vs. 25%) and very good partial response (VGPR) or better ( 79% vs. 53%). 1As part of the study, patient health, functional capacity, symptoms, psychosocial well-being and life satisfaction were assessed through measures to assess changes in quality of life related to health using the questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) on the quality of life and the study EQ-5D-5L on the health profile of EuroQol. 2

The most common adverse events during treatment grade 3/4 for daratumumab-Rd (≥10 percent) included neutropenia (50%), lymphopenia (15%), pneumonia (14%), and anemia (12%). 1 Infusion-related reactions occurred in 41% of patients receiving daratumumab-Rd, of whom 3% were grade 3/4. 1 The incidence of the second primary invasive malignancy was 3% in the daratumumab-Rd group compared to 4% in the Rd group alone. 1 EISTs leading to death were 7% in the daratumumab-Rd group, compared to 6% in the Rd group. 1The safety profile of daratumumab was consistent with previous studies. 1,3,4,5,6,7

Daratumumab-Rd is being reviewed by the US Food and Drug Administration (FDA) as part of the Real-Time Oncology Review (RTOR) pilot program.

In Europe, daratumumab is indicated: 8

in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplantation
as monotherapy for the treatment of adult patients with recurrent and refractory multiple myeloma whose previous treatment included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated progression of the disease during the last treatment
in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
#END#

About the MAIA 2 study
The randomized, open-label, multi-center Phase 3 study included 737 newly diagnosed patients with multiple myeloma eligible for high-dose chemotherapy and GATS, aged 45 to 90 years (median age 73). Patients were randomized to receive the combination of daratumumab-Rd or Rd alone in 28-day cycles. In the patients treated with daratumumab-Rd combination, patients received weekly 16 milligrams of daratumumab per kilogram (mg / kg) intravenously during cycles 1 and 2, every other week during cycles 3 to 6, and every 4 weeks from cycle 7. Patients in the daratumumab-Rd and Rd alone arm received lenalidomide 25 mg on days 1 to 21 of each 28-day cycle, and a weekly dose of 40 mg dexamethasone in each cycle. Patients from both treatment arms continued until disease progression or an unacceptable degree of toxicity.

About Daratumumab
Daratumumab is a novel genus that targets the CD38 gene, a surface protein that is highly expressed in multiple myeloma cells, regardless of the stage of the disease. 9,10 Daratumumab is thought to induce rapid tumor cell death through numerous immune-mediated mechanisms of action, including complement-dependent cytotoxicity and antibody-dependent cellular phagocytosis, as well as apoptosis in the course of time. which a series of cell steps inside the cell result in the death of the cell. 11A subset of suppressor cells derived from myeloid cells (CD38 + MDSCs), CD38 + regulatory T cells, and CD38 + B cells decreased with daratumumab treatment. 11 Daratumumab is being evaluated in a comprehensive clinical development program across a range of multiple myeloma therapies, including first-line and post-relapse therapies. 2,12,13,14,15,16,17,18 Ongoing or planned studies are being conducted to evaluate its potential in the treatment of other hematologic malignant and pre-malignant diseases in which CD38 is expressed, such as indolent myeloma . 19,20 For more information, please consultwww.clinicaltrials.gov .

For more information about daratumumab, please see the Summary of Product Characteristics at View Source .

In August 2012 , Janssen Biotech, Inc. and Genmab A / S entered into a worldwide agreement that granted Janssen an exclusive license to develop, manufacture and market daratumumab. 21

About Multiple Myeloma Multiple
myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterized by excessive proliferation of plasma cells. 22 More than 48,200 people have been diagnosed with multiple myeloma in Europe in 2018, and more than 30,800 patients have died. 23 Nearly half of newly diagnosed patients do not achieve five-year survival, 24 and nearly 29% of multiple myeloma patients die within one year of diagnosis. 25

Although the treatment may lead to a remission, unfortunately, patients will most likely experience a relapse because there is currently no cure. 26 The refractory multiple myeloma is a disease which progresses within 60 days following the last treatment of the patient. 27,28 Recurrent cancer refers to the return of the disease after a period of initial, partial or complete remission. 29While some patients with multiple myeloma have absolutely no symptoms, the majority of them are diagnosed because of symptoms that may include bone problems, low blood counts, elevated calcium levels, kidney problems, or infections. . 30 Patients who relapse after treatment with standard therapies, including IP and immunomodulatory agents have a poor prognosis and have few treatment options available. 31

On March 25, 2019 Castle Biosciences, Inc., a cancer diagnostics company providing personalized genomic information to improve cancer management decisions, reported that it will present five-year outcomes from a prospective, multicenter study showing that DecisionDx-UM accurately predicts metastatic risk for patients with uveal melanoma and is used by physicians to make patient management decisions based on risk categories determined by the test (Press release, Castle Biosciences, MAR 25, 2019, View Source [SID1234534606]). The study will be presented at the International Society of Ocular Oncology (ISOO) Biennial Conference held March 22-26 in Los Angeles CA.

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The CLEAR study (Clinical Application of DecisionDx-UM Gene Expression Assay Results) was designed to track clinical management and metastatic outcomes of patients with uveal melanoma who were tested with the DecisionDx-UM gene expression profile (GEP) test as part of their diagnostic work-up.

"An accurate understanding of metastatic risk is critical to guiding surveillance planning for patients with uveal melanoma since clinicopathologic staging alone is insufficient," commented investigator Thomas M. Aaberg, Jr., M.D., Assistant Clinical Professor at Michigan State University Medical School and ocular oncologist with Retina Specialists of Michigan, who presented the study. "The results from the CLEAR study are consistent with previous publications and confirm the accuracy and clinical utility of the DecisionDx-UM test in clinical practice."

Study Highlights:

89 patients from four centers were enrolled between March 2011 and January 2017. Median follow-up time for patients without metastasis was 4.7 years.
49 patients (55%) had a low-risk Class 1 test result; 40 patients (45%) had a high-risk Class 2 test result.
All patients with Class 2 test results were managed with high intensity surveillance (imaging and/or liver function tests every 3-6 months), while 80% of Class 1 patients were managed with low intensity surveillance (imaging and/or liver function tests at a maximum of once each year) (p<0.0001).
Overall, three (6%) Class 1 patients and 22 (55%) Class 2 patients developed metastasis (p<0.0001). Median time to metastasis was 3.2 years for Class 1 and 2.5 years for Class 2.
Five-year metastasis-free survival rates were 92% for Class 1 and 42% for Class 2 (p<0.0001).
In multivariate analysis including age, ciliary body involvement, largest basal diameter and tumor thickness, the DecisionDx-UM Class 2 result was the only statistically significant predictor of metastasis (p<0.0001).
These findings are consistent with results from previously published prospective studies documenting the accuracy of DecisionDx-UM and impact on patient management.
About DecisionDx-UM

DecisionDx-UM is a GEP test that uses an individual patient’s tumor biology to predict individual risk of metastasis. DecisionDx-UM is the standard of care in the management of uveal melanoma in the majority of ocular oncology practices. Since 2009, the American Joint Committee on Cancer (AJCC; v7 and v8) has included GEP testing for the identification of Class 1 and 2 as a prognostic factor recommended for clinical care. In 2018, the National Comprehensive Cancer Network (NCCN) published guidelines on uveal melanoma that include the DecisionDx-UM test results of Class 1A, Class 1B and Class 2B as prognostic factors to guide clinical care. DecisionDx-UM is the only prognostic test for uveal melanoma that has been validated in prospective, multi-center studies. In addition, the DecisionDx-UM test result has been shown to be a superior predictor of metastasis compared to chromosome 3 status, mutational status, AJCC stage, and cell type, as demonstrated in multiple studies.

It is estimated that nearly 8 in 10 patients diagnosed with uveal melanoma in the U.S. receive the DecisionDx-UM test as part of their diagnostic workup. More information about the test and disease can be found at www.MyUvealMelanoma.com.

On March 25, 2019 Genomic Health, Inc. (NASDAQ: GHDX) reported that new data presented at the 16th St.Gallen International Breast Cancer Conference in Vienna reinforce the utility of the Oncotype DX Breast Recurrence Score test to optimize chemotherapy recommendations in patients with early-stage breast cancer with or without lymph node involvement (Press release, Genomic Health, MAR 25, 2019, View Source [SID1234534605]).

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The important role of genomic testing to optimize patient outcomes in early-stage breast cancer was discussed in a debate between leading international breast cancer specialists during the St. Gallen Conference. The experts presented several case studies showing that genomic testing adds value beyond clinical pathological factors, and they agreed that there are substantial differences between the available tests.

"Only a test such as Oncotype DX that has been developed specifically to be predictive of chemotherapy benefit can identify the right treatment for the right patient," said Prof. Joseph Gligorov, M.D., of the Breast Cancer Expert Center at the APHP-Tenon Hospital in Paris, who participated in the panel discussion. "The practice-changing precision made possible by such a test can lead to improved quality of care and survival among breast cancer patients, as well as reduced waste of healthcare resources by directing chemotherapy only to patients who have a high likelihood of deriving substantial benefit."

Oncotype DX Data Presentations
An updated analysis of the Clalit Health Services registry, the largest health services organization in Israel, was presented at the Conference. This analysis examined the medical records of more than 1,300 patients with node-negative breast cancer applying the Recurrence Score cut point determined by the landmark TAILORx study. The findings showed that use of chemotherapy was aligned with Oncotype DX test results and that patients with Recurrence Score results up to 25, the vast majority of whom were treated with hormonal therapy alone, had excellent outcomes at 10 years, with low rates of distant recurrence.

Also presented at the Conference was real-world evidence from a study in more than 80,000 patients, based on an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) registry program of the National Cancer Institute (NCI). The findings confirmed that the Recurrence Score result is predictive of chemotherapy benefit in patients with node-negative disease (p=0.009), with no chemotherapy benefit in patients with Recurrence Score results up to 25. In patients with node-negative disease and Recurrence Score results up to 25 not treated with chemotherapy, the Breast Cancer Specific Survival (BCSS) was greater than 98 percent at nine years. In patients with node-positive disease not treated with chemotherapy and Recurrence Score results less than 18, BCSS was greater than 97 percent at nine years.

Importantly, this real-world evidence reinforces the paradigm established by the TAILORx study, which provided definitive information on how to treat women with node-negative early-stage breast cancer based on their Recurrence Score results. TAILORx, the largest randomized adjuvant breast cancer treatment trial ever conducted, identified the vast majority of women who receive no substantial benefit from chemotherapy, as well as the important minority for whom chemotherapy can be life-saving.

Results of two decision impact studies from the UK and the Czech Republic, highlighting the value of Oncotype DX to personalize and improve the quality of clinical decisions, also were presented at the Conference. In the UK study, clinical practice results from 582 patients with node-positive disease (one to three positive lymph nodes) showed that chemotherapy recommendations changed in a significant proportion of patients following testing with Oncotype DX. In particular, the test allowed more than 60 percent of patients to be spared chemotherapy and its associated short- and long-term side-effects. Conversely, the test identified 23 patients who were initially advised to undergo only endocrine therapy, but whose treatment was changed to add chemotherapy based on their Recurrence Score result. Without testing, these patients would not have received potentially life-saving chemotherapy treatment.

"In serving more than one million cancer patients around the world with Oncotype DX, we are delivering on the promise of precision medicine by improving outcomes, while saving healthcare systems around the world billions of dollars," said Rick Baehner, M.D., chief medical officer, Genomic Health. "These new data, based on results from thousands of patients in the U.S. and Europe, further reinforce the value and need for broader global access to Oncotype DX testing."

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. The company’s flagship product, the Oncotype DX Breast Recurrence Score test, is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Genomic Health. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

On March 25, 2019 VBL Therapeutics (Nasdaq: VBLT), reported that the Company will present data on its Phase 3 drug candidate VB-111, at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held March 29 – April 3, 2019 at Georgia World Congress Center in Atlanta, Georgia (Press release, VBL Therapeutics, MAR 25, 2019, View Source [SID1234534604]). VB-111 is a first-in-class, targeted anti-cancer gene-therapy biologic with broad potential to treat a wide range of solid tumors. In addition, the company will provide a corporate overview at the H.C. Wainwright Global Life Sciences Conference to be held April 7 – 9, 2019 at the Grosvenor House, a JW Marriott Hotel in London, UK.

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The AACR (Free AACR Whitepaper) Annual Meeting – Presentation Details:
Title: Ofranergene Obadenovec (VB-111), an anti-cancer gene therapy, induces immunologic responses in solid tumors transforming ‘cold’ tumors to ‘hot’ tumors
Session Category: Immunology
Session Title: Immunomodulators and Response to Therapy
Date: Wednesday Apr 3, 2019
Time: 8:00 AM – 12:00 PM Eastern Time
Session Location: Exhibit Hall B, Poster Section 24
Poster Board Number: 2
Abstract Number: 4979

HCW Global Life Sciences Conference – Presentation Details:

Date:Monday, April 8
Time: 15:40 – 16:00 BST

On March 25, 2019 NantKwest (Nasdaq:NK), a leading clinical-stage, natural killer cell based therapeutics company, reported that Patrick Soon-Shiong, MD, the company’s Chairman & CEO, on March 21, 2019, exercised 17,589,250 warrants with an exercise price of $1.9984 and 1,851,000 options with an exercise price of $2.1983, representing an aggregate cash exercise price of $39.2 million (Press release, NantKwest, MAR 25, 2019, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-chairman-ceo-dr-patrick-soon-shiong-exercises-39?field_nir_news_date_value[min]=2019 [SID1234534603]).

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In commenting on the exercise of the warrants and options, Dr. Soon-Shiong said the following: "Since the launch of NantKwest in 2015, the company has made remarkable progress in the development of a true, ‘off-the-shelf’ and ‘ready-to-use’ Natural Killer (NK) cell therapy that could be shipped on an ‘as needed basis,’ just about anywhere in the world. We have successfully established a truly off-the-shelf, cryopreserved product and are now ready to embark on pivotal trials. This advanced manufacturing capability combined with our ability to develop NK cells with high killing activity provides us with a distinct advantage as the leading company developing an immediately available NK cell therapy for patients with cancer."

Dr. Soon-Shiong continued, "My commitment and confidence in the future success of NantKwest has never been stronger. I firmly believe that the natural killer cell represents the missing link in our war against cancer. I believe that only by orchestrating the activity of the natural killer cell, the innate immune system, as well as the killer T cell, the adaptive immune system, could we achieve long lasting responses to immunotherapy. NantKwest represents this next generation of cell therapy with the potential to achieve activation of the memory T and NK cell, the holy grail of immunotherapy. Contributing an additional $39.2 million to the financial resources of NantKwest will enable the rapid opening of multiple clinical trial sites for the Phase 2 trial of off-the-shelf activated natural killer cells (haNK cells), combined with an IL-15 cytokine (N-803) which may proliferate NK and T cells, to treat refractory patients suffering from a deadly disease, Merkel Cell Carcinoma. In addition, preclinical data of the world’s first targeted off-the-shelf haNK cells (t-haNK) are highly encouraging and we are planning the first in human trials of both PD-L1 t-haNK and CD-19 t-haNK (targeted-haNKs) this year."

Dr. Soon-Shiong provided an update on the haNK and t-haNK programs at his keynote address to the scientific community at "The Innate Killer Summit" in San Diego on March 20, 2019.