On May 18, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the Phase III POLLUX study (MMY3003) of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.37 (95% CI 0.27-0.52), p < 0.0001) (Press release, Genmab, MAY 18, 2016, View Source [SID:1234512523]).

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Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone.

Overall, the safety profile of daratumumab in combination with lenalidomide and dexamethasone was manageable and consistent with the known safety profile of the lenalidomide and dexamethasone combination, with the ongoing Phase II study, GEN503, which evaluated safety and efficacy of daratumumab in combination with lenalidomide and dexamethasone as well as daratumumab monotherapy.

Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended that the data be unblinded. Patients originally assigned to the lenalidomide plus dexamethasone alone treatment group will be offered the option of receiving daratumumab monotherapy following confirmed disease progression. All patients will continue to be monitored for safety and overall survival. Further analysis of the safety and efficacy data is underway and will be shared with the health authorities. Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will engage in a dialogue with health authorities about the potential for a regulatory submission for this indication. The trial results are also aimed to be presented at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) as well as submitted for publication in a peer-reviewed journal.

"The POLLUX study is the second key Phase III study of daratumumab to meet the primary endpoint at a pre-planned interim analysis and demonstrates a favorable benefit-risk ratio. We have now seen that daratumumab can potentially be used to effectively treat relapsed or refractory multiple myeloma in combination with either lenalidomide or bortezomib, two standard of care multiple myeloma treatments," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the study
The Phase III POLLUX study enrolled 569 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid), or lenalidomide and dexamethasone alone. The primary endpoint of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,850 new patients were estimated to be diagnosed with multiple myeloma and approximately 11,240 people would die from the disease in the U.S. in 2015.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,8 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,8 antibody-dependent cellular phagocytosis9,10 and antibody-dependent cellular cytotoxicity.7,8 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs)7, all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.7

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.

On May 18, 2016 Fortress Biotech (NASDAQ: FBIO), a biopharmaceutical company dedicated to acquiring, developing and commercializing novel pharmaceutical and biotechnology products, reported positive data from the Phase 1/2 study of CNDO‐109‐Activated Allogeneic Natural Killer (NK) Cells in patients with acute myeloid leukemia (AML) in their first complete remission who are at a high risk of relapsing (Press release, Fortress Biotech, MAY 18, 2016, View Source [SID:1234512522]). The data were presented yesterday in an oral session at the Innate Killer Summit 2016 in San Diego, CA.

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Dr. Lindsay A. Rosenwald, Chairman, President and CEO of Fortress, said, "We are very pleased by the early safety profile demonstrated by CNDO‐109‐Activated NK Cells.  Additionally, while designed primarily to determine the safety of CNDO‐109 in patients who were already in remission, we were encouraged to see three high‐risk patients treated at the higher dose cohorts remain in complete remission for approximately two years." Dr. Rosenwald continued, "We would like to thank the investigators who participated in this Phase 1/2 study for their efforts on this important research program."

CNDO‐109‐Activated Allogeneic Natural Killer (NK) Cells   CNDO‐109 is a lysate (disrupted CTV‐1 cells, cell membrane fragments, cell proteins and other cellular components) that activates donor NK cells ex vivo. Fortress acquired exclusive worldwide rights to develop and commercialize CNDO‐109 activated NK cells for the treatment of cancer from University College London Business.

About Acute Myeloid Leukemia (AML)
AML is one of the deadliest and most common types of acute leukemia in adults. According to a Decision Resources report, there are more than 43,000 cases worldwide, primarily afflicting elderly and relapsed and refractory populations. Once diagnosed with AML, patients typically receive induction and consolidation chemotherapy, with the majority achieving complete remission. However, roughly 70–80 percent of patients who achieve first complete remission will relapse, and the overall five‐year survival rate is less than 25 percent.  

On May 18, 2016 MacroGenics, Inc. (Nasdaq: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as various autoimmune disorders and infectious diseases, reported a global collaboration and license agreement for MGD015, a preclinical bispecific molecule, with Janssen Biotech, Inc (Press release, MacroGenics, MAY 18, 2016, View Source [SID:1234512511]).

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This product candidate incorporates MacroGenics’ proprietary Dual-Affinity Re-Targeting, or DART, platform to simultaneously target CD3 and an undisclosed tumor target for the potential treatment of various hematological malignancies and solid tumors.

Under the terms of the agreement and subject to the termination or expiration of any applicable waiting periods under the Hart-Scott-Rodino Act, MacroGenics will receive a $75 million upfront license fee. Janssen will complete IND-enabling activities and be fully responsible for future clinical development of MGD015. Assuming successful development and commercialization, MacroGenics could receive up to an additional $665 million in clinical, regulatory and commercialization milestone payments. MacroGenics may elect to fund a portion of late-stage clinical development in exchange for a profit share in the U.S. and Canada. If commercialized, MacroGenics would be eligible to receive double-digit royalties on any global net sales and has the option to co-promote MGD015 with Janssen in the U.S.

"MGD015 is a promising product candidate that employs MacroGenics’ proprietary DART platform to enable a potent redirected T-cell killing mechanism with ‘off-the-shelf’ convenience. This approach is already being evaluated in five other clinical-stage DART programs," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Janssen represents the ideal partner for MGD015, given its track record of successfully developing and commercializing transformative oncology therapies. This collaboration builds on an existing Janssen relationship around MGD011, a DART molecule targeting CD19 and CD3, which is now being evaluated in the clinic."

About MGD015

MGD015 is designed to redirect T cells, via their CD3 component, to eliminate cells which overexpress an undisclosed antigen in various hematological malignancies and solid tumors. MacroGenics has demonstrated that MGD015 is able to kill these targeted cells both in vitro and in vivo, with high response rates in several mouse tumor xenograft models. In addition, this product candidate and the Company’s other DART molecules that redirect T cells against cancer targets are manufactured using a conventional antibody platform without the complexity of having to genetically modify T cells from individual patients as required by approaches such as chimeric antigen receptor (CAR) T-cells.

On May 18, 2016 Novartis reported that the MONALEESA-2 independent Data Monitoring Committee recommended stopping the trial early as results of a pre-planned interim analysis showed the trial met the primary endpoint of clinically meaningful improvement in PFS[1] (Press release, Novartis, MAY 18, 2016, View Source [SID:1234512510]).

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MONALEESA-2 is a pivotal Phase III trial of LEE011 (ribociclib), a cyclin dependent kinase inhibitor (CDK4/6), in combination with letrozole, compared to letrozole alone in postmenopausal women who had received no prior therapy for their hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer[1].

"We are excited that these results validate our belief that LEE011 in combination with letrozole can be a beneficial treatment option for women diagnosed with HR+/HER2- advanced breast cancer," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "Novartis is dedicated to continuing to discover and develop innovative targeted therapies that help improve and extend the lives of women living with this disease."

As part of the company’s ongoing commitment to addressing the needs of patients living with advanced breast cancer, Novartis will be evaluating possible expanded access programs in some regions to help ensure women who may benefit from LEE011 have access to it.

The adverse events observed with LEE011 in combination with letrozole in MONALEESA-2 were generally consistent with their respective known adverse event profiles[1].

The MONALEESA-2 trial will continue to assess overall survival data. Detailed efficacy and safety data will be submitted for presentation at a major medical congress and Novartis will begin discussions with global health authorities about regulatory filings.

About MONALEESA-2
MONALEESA-2 (Mammary ONcology Assessment of LEE011’s Efficacy and SAfety-2) is a Phase III randomized, double blind, placebo controlled, multicenter global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer[1].

The trial was conducted at 294 clinical trial sites globally and randomized 668 patients in a 1:1 ratio stratified by the presence of liver and/or lung metastases[1]. Patients received LEE011 600 mg/daily (three weeks on and one week off), or placebo, in combination with letrozole 2.5 mg/daily per the approved label[1].

The primary endpoint of the trial was PFS[1]. Secondary endpoints included: overall survival, overall response rate, clinical benefit rate, health-related quality of life, safety and tolerability[1].

About LEE011 (ribociclib)
LEE011 (ribociclib) is a cyclin dependent kinase inhibitor (CDKi), a new class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated in a cell, can enable cancer cells to grow and divide too quickly.

LEE011 has been studied in non-clinical models and is currently being evaluated in combination with additional endocrine agents as part of the MONALEESA clinical trial program. LEE011 is not approved for any indication in any market at this time.

The MONALEESA-3 trial is evaluating LEE011 in combination with fulvestrant compared to fulvestrant alone in men and post-menopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. The MONALEESA-7 trial is investigating LEE011 in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in pre-menopausal women with HR+/HER2- advanced breast cancer who have not previously received endocrine therapy. Both Phase III programs, MONALEESA-3 and MONALEESA-7 are recruiting patients worldwide.

LEE011 was developed by Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About Novartis in advanced breast cancer
For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients and improving clinical practice in partnership with the global community[1]. With one of the most diverse breast cancer pipelines and the largest number of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease[1].

About advanced breast cancer
Advanced breast cancer comprises metastatic breast cancer (stage IV) and locally advanced breast cancer (stage III)[2]. Metastatic breast cancer is the most serious form of the disease and occurs when the cancer has spread to other parts of the body, such as the brain, bones or liver[2]. Locally advanced breast cancer occurs when the cancer has spread to lymph nodes and/or other tissue in the area of the breast, but not to distant sites in the body[2].

HR+/HER2- advanced breast cancer is the most common type of advanced breast cancer, with an estimated 220,000 women diagnosed globally each year[3],[4]. HR+ advanced breast cancer is a group of cancers that express receptors for certain hormones, such as estrogen and progesterone[5]. Cancer cell growth can be driven by these hormones[5].

On May 18, 2016 AstraZeneca reported that Lynparza (olaparib) in combination with paclitaxel chemotherapy, compared with paclitaxel chemotherapy alone, did not meet the primary endpoint of overall survival (OS) in the Phase III GOLD trial in advanced gastric cancer patients, in either the overall population or patients whose tumour tested negative for Ataxia-Telangectasia Mutated (ATM) protein (Press release, AstraZeneca, MAY 18, 2016, View Source [SID:1234512499]). Whilst there was a numerical survival trend in the Lynparza plus paclitaxel arm, it did not meet statistical significance.

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "While there was a numerical trend for survival benefit with Lynparza plus paclitaxel in the GOLD trial, we are disappointed that this did not reach statistical significance. The particular regimen in the GOLD study, at a low dose and in combination with chemotherapy, differs from other Phase III trials in the Lynparza programme. We look forward to presenting the GOLD data and remain confident in Lynparza’s clinical activity in a range of tumour types, including its approved use in BRCA-mutated ovarian cancer."

GOLD was a randomised, double-blinded, placebo-controlled, multicentre Phase III trial to assess the efficacy and safety of Lynparza in combination with paclitaxel, compared with paclitaxel alone. The trial enrolled Asian patients with advanced HER2-negative gastric cancer (including the gastro-oesophageal junction) who had progressed following 1st-line therapy. The trial, conducted in China, Japan, South Korea and Taiwan where gastric cancer is particularly prevalent, enrolled a total of 525 patients – 18% of whom had tumours that tested ATM negative by immunohistochemistry (IHC). Lynparza was given orally at a dose of 100mg twice daily in combination with paclitaxel IV infusion over 1 hour at 80mg/m2 weekly on days 1, 8 and 15 of a 28 day schedule.

The reported incidence of adverse events for Lynparza in combination with paclitaxel compared with paclitaxel alone was similar.

A full evaluation of the data is ongoing and the results will be submitted for presentation at an upcoming medical meeting.

Lynparza is approved in over 40 countries for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.

NOTES TO EDITORS

About Gastric Cancer

Gastric and Gastroesophageal Junction (GEJ) adenocarcinomas account for around 84% of all cancers of the stomach. The incidence of gastric cancer (GC) is disproportionally high in East Asia, where annual incidence is around 9 times higher than those in the G6 countries combined.&supl;

About Lynparza

Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is the first PARP inhibitor to be approved by regulatory authorities in the EU and US for the treatment of women with BRCA-mutated (BRCAm) ovarian cancer.

About AstraZeneca in Oncology AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least 6 new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms — immuno-oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates — and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.