On May 26, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that following a planned review, the DMC has recommended that the Phase Ib/II study (CALLISTO/LUC2001) of daratumumab in combination with atezolizumab versus atezolizumab monotherapy in patients with previously treated advanced or metastatic non-small cell lung cancer should be terminated (Press release, Genmab, MAY 26, 2018, View Source [SID1234526923]). In addition the phase I MMY2036 study of daratumumab plus JNJ-63723283, an anti PD-1 antibody in patients with multiple myeloma will be discontinued.

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The DMC determined that there was no observed benefit within the combination treatment arm, daratumumab plus atezolizumab, over atezolizumab monotherapy, and recommended termination of the study. In addition to the lack of benefit, the DMC noted a numerical increase in mortality-related events in the combination arm.

Based on these findings, Janssen has made the decision also to discontinue the MMY2036 study, which was evaluating a combination of daratumumab and anti-PD-1 (JNJ-63723283) in patients with Multiple Myeloma. Janssen has informed Health Authorities about these events and has contacted its partner companies conducting daratumumab and anti-PD-(L)1 combination studies to discuss ceasing enrollment and dosing of the combination while the data is being further investigated.
In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

"While we are disappointed that the studies will be discontinued, Genmab fully supports Janssen’s decision as patient safety is paramount in drug development. We look forward to gaining a better understanding of the data upon further analysis. We are pleased that the development program for daratumumab remains expansive and continues to benefit patients with Multiple Myeloma" said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the LUC2001 study
This randomized, multicenter, Phase Ib/II study includes 98 patients with previously treated advanced or metastatic NSCLC. Patients will be randomized to receive daratumumab at 16 milligrams per kilogram (mg/kg) weekly for 3 cycles and on day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1,200 mg on day 2 of Cycle 1 and on day 1 of every 21-day cycle thereafter. Patients will continue to receive treatment until disease progression or unacceptable toxicity. Patients in the atezolizumab monotherapy arm with confirmed disease progression will be eligible to crossover to the daratumumab plus atezolizumab arm, if they meet the crossover eligibility criteria. The primary endpoint of the study is percentage of patients with ORR, defined as percentage of patients with PR or CR as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
About MMY2036 study
This randomized, multicenter, multiphase study includes up to 386 patients with relapsed or refractory multiple myeloma. Approximately 6 subjects will be enrolled in Part 1 (a safety run-in cohort) followed by 80 subjects randomly assigned in a 1:1 ratio to the 2 treatment arms in Part 2 (Phase 2). After all subjects in Part 2 are followed-up for approximately 4 months, it will be determined, based on review of all available data, whether to initiate Part 3 (Phase 3) of this study, where an additional 300 subjects will be randomly assigned in a 1:1 ratio to the 2 treatment arms. Patients are randomized to receive JNJ 63723283 (PD-1 antibody) administered in combination with daratumumab, compared with daratumumab alone. Daratumumab is dosed at 16 milligrams per kilo (mg/kg) weekly for 8 weeks, then once every other week for 16 weeks; then once every 4 weeks. JNJ 63723283 is dosed at 240 milligrams IV fixed dose during week 1 on cycle 1 (28 days) day 2, cycle 1 day 15, then every 2 weeks thereafter. The primary endpoints of the study are in Part 1: number of participants with adverse events (AE) Including Dose-Limiting Toxicities (DLTs) during cycle 1. An adverse event is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. In Part 2: Overall Response Rate (ORR) as per International Myeloma Working Group (IMWG) criteria and in Part 3: Progression-Free Survival (PFS) which is the time from treatment start until the disease get worse.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use 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 and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. 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. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On May 25, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported positive overall survival (OS) results for the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi (durvalumab) in patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease had not progressed following platinum-based chemotherapy concurrent with radiation therapy (CRT) (Press release, AstraZeneca, MAY 25, 2018, View Source [SID1234526893]).

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A planned interim analysis conducted by an Independent Data Monitoring Committee concluded that the trial has met its second of two primary endpoints by showing statistically-significant OS benefit with clinically-meaningful improvement in patients receiving Imfinzi compared to placebo. The safety and tolerability profile for Imfinzi was consistent with that reported at the time of the progression-free survival (PFS) analysis. AstraZeneca plans to present results from the PACIFIC trial at a forthcoming medical meeting.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The readout of positive overall survival data at the interim analysis of the PACIFIC trial provides additional compelling evidence of the clinical benefit that Imfinzi can offer patients in this earlier stage of lung cancer. We look forward to sharing these results with Health Authorities to support ongoing regulatory interactions and to update the Imfinzi label with these important data."

In May 2017, AstraZeneca announced that the PACIFIC trial met its first primary endpoint of PFS by demonstrating a median improvement of 11.2 months vs. placebo, as assessed by blinded independent central review.

Imfinzi is currently approved in the US and Canada for the treatment of patients with unresectable Stage III NSCLC who had not progressed following platinum-based chemoradiation therapy and under regulatory review in the EU, Japan and other jurisdictions with expected decisions in the second half of 2018.

About Stage III NSCLC

Stage III (locally-advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to distant organs.

Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-eight countries (China, France, Germany, Italy, Japan, Spain, UK, US) in 2017. The majority of Stage III NSCLC patients are diagnosed with unresectable tumours. Before the PACIFIC trial, the standard of care was chemotherapy and radiation therapy, followed by active surveillance to monitor for progression.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in patients with Stage III unresectable NSCLC whose disease has not progressed following platinum-based chemoradiation therapy (CRT).

The trial is being conducted in 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, overall response rate, and duration of response.

About Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Earlier this month, Imfinzi received approval in Canada for the treatment of patients with unresectable Stage III NSCLC following chemoradiation therapy (CRT). In February 2018, Imfinzi received regulatory approval from the US FDA for the treatment of patients with unresectable Stage III NSCLC who had not progressed following concurrent platinum-based CRT.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with chemotherapy, radiation therapy, small molecules, and tremelimumab, an anti-CTLA4 monoclonal antibody, as a first-line treatment for patients with NSCLC, small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.

About AstraZeneca in Lung Cancer

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer across all stages of disease and lines of therapy. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa and Tagrisso and ongoing FLAURA, ADAURA and LAURA Phase III trials. Our extensive late-stage immuno-oncology programme focuses on 75-80% of patients with lung cancer without a known genetic mutation. The portfolio includes Imfinzi, an anti-PDL1 antibody, which is in development as monotherapy (ADJUVANT BR.31, MYSTIC and PEARL trials) and in combination with tremelimumab and/or chemotherapy (MYSTIC, NEPTUNE, CASPIAN, and POSEIDON trials).

About AstraZeneca’s Approach to Immuno-Oncology (IO)

Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical trial programme that includes Imfinzi (anti-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our Oncology pipeline, and with those of our research partners, may provide new treatment options across a broad range of tumours.

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 six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advancing Oncology as a growth driver for AstraZeneca, 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, Tumour Drivers 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.

On May 25, 2018 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada), reported that the U.S. Food and Drug Administration (FDA) has extended the action date for the supplemental New Drug Application (sNDA) for the multiple receptor tyrosine kinase inhibitor LENVIMA (generic name: lenvatinib mesylate) for the potential first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) (Press release, Eisai, MAY 25, 2018, View Source [SID1234526896]).

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The FDA has indicated that the extension of the Prescription Drug User Fee Act (PDUFA) date is needed to allow additional time for review of the application. The agency expects to complete the review on or before August 24, 2018, thus extending the target action date by a standard extension period of three months from the original PDUFA action date of May 24, 2018.
Eisai, as the marketing authorization holder, is working closely with the FDA to support the continued review of this application.

LENVIMA is approved by the U.S. FDA for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). LENVIMA is also approved by the U.S. FDA in combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy.

Media Inquiries:
Eisai Co., Ltd.

Public Relations Department
+81-(0)3-3817-5120

About LENVIMA (lenvatinib mesylate)
Discovered by Eisai, LENVIMA is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.
Currently, LENVIMA is approved as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 40 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma.
LENVIMA is approved as a monotherapy for unresectable hepatocellular carcinoma in Japan (March 2018).
Eisai has submitted applications for an indication covering hepatocellular carcinoma in the United States and Europe (July 2017), China (October 2017), Taiwan (December 2017) and other countries

On May 25, 2018 IMMUTEP Presented 3rd Annual Advances in Immuno-Oncology Congress Presentation (Presentation, Immutep, MAY 25, 2018, View Source [SID1234526995]).

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On May 25, 2018 IntegraGen reported it will be in attendance at 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) being held in Chicago from June 1st to June 5th (Press release, Integragen, MAY 25, 2018, View Source [SID1234526899]). The Annual ASCO (Free ASCO Whitepaper) Meeting brings together more than 32,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field.

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