On July 23, 2018 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported it has entered into a collaboration agreement with Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate Leap’s GITR agonist, TRX518, in combination with avelumab*, a human anti-PD-L1 IgG1 monoclonal antibody, and chemotherapy (Press release, Leap Therapeutics, JUL 23, 2018, View Source;p=RssLanding&cat=news&id=2359396 [SID1234528762]).

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Under the terms of the collaboration, Leap will be conducting a Phase I/II clinical trial in advanced solid tumors including expansion populations in patients with relapsed/refractory ovarian, breast, and prostate cancers. The study is expected to begin enrolling patients in the first quarter of 2019.

"The combination of TRX518 with anti-PD-L1 immunotherapy and cyclophosphamide has a solid scientific rationale and we look to build upon our early clinical and preclinical data highlighting the potential benefits of such a combination," commented Cynthia Sirard, M.D., Vice President, Clinical Development of Leap Therapeutics.

"TRX518 has demonstrated encouraging potential with early clinical activity in patients with advanced solid tumors," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "This collaboration with Leap Therapeutics to evaluate TRX518 in combination with avelumab gives us the opportunity to investigate a potential novel immunotherapy treatment regimen as we pursue our mission of improving outcomes for patients living with hard-to-treat cancers."

"Combination therapy remains a major focus in our clinical development program for avelumab in an effort to advance the treatment landscape for patients with challenging cancers," said Alise Reicin, Head of Global Clinical Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "Through our collaboration with Leap Therapeutics, we are eager to further understand the potential of this novel immunotherapy combination in this patient population."

Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.

*Avelumab is under clinical investigation for treatment of solid tumors and hematological malignancies in combination with TRX518 and has not been demonstrated to be safe and effective for these uses. There is no guarantee that avelumab will be approved for solid tumors or hematological malignancies by any health authority worldwide.

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and over 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Approved Indications in the US**

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) mMCC in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications were approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information from the US FDA Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

On July 23, 2018 Diplomat Pharmacy, Inc. (NYSE: DPLO), repported that it will release its second-quarter 2018 operating results after market close Monday, Aug. 6, with a conference call to follow at 5 p.m. ET (Press release, Diplomat Speciality Pharmacy, JUL 23, 2018, View Source [SID1234527828]).

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Shareholders and interested participants can listen to a live broadcast by calling 833.286.5805 (647.689.4450 for international callers) and entering the participation code 1842529, starting about 15 minutes before the call. A live webcast of the conference call will be available on the investor relations section of Diplomat’s website at ir.diplomat.is. The site will host an audio recording and supplemental investor information for 90 days.

On July 23, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq:SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported that data on the adjuvant treatment of women with triple-negative breast cancer (TNBC) with the combination of trastuzumab (Herceptin) +/-nelipepimut-S (NeuVax) will be presented as a Proffered Paper in an oral presentation at the 2018 Annual Meeting of the European Society for Medical Oncology October 19-23 in Munich, Germany (Press release, Sellas Life Sciences, JUL 23, 2018, View Source;Herceptin-at-Upcoming-European-Society-for-Medical-Oncology-ESMO-2018-Meeting/default.aspx [SID1234527830]).

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The abstract, "Pre-specified interim analysis of a randomized phase 2b trial of trastuzumab + nelipepimut-S (NeuVax) vs trastuzumab for the prevention of recurrence demonstrates benefit in triple negative (HER2 low-expressing) breast cancer patients," describes research undertaken at Cancer Insight, LLC by a team of clinicians-scientists led by COL (ret) George E. Peoples, MD, FACS, the principal investigator for the study.

Data will be presented from a prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial (IST) of Herceptin +/- NeuVax in HER 1+/2+ breast cancer patients in the adjuvant setting to prevent recurrences. As previously announced, a pre-specified interim analysis of safety and efficacy conducted by the study independent data safety monitoring board (DSMB), demonstrated a clinically meaningful and statistically significant difference between the TNBC cohort of patients and the control arm with a hazard ratio of 0.26, p-value = 0.023, in favor of the NeuVax + Herceptin combination compared to Herceptin alone. The analysis also showed an adverse event profile with no notable differences between treatment arms and no additional cardiotoxicity in the NeuVax + Herceptin arm. Based on these positive results, the DSMB recommended to expeditiously seek regulatory guidance from the U.S. Food and Drug Administration for further development of the combination of NeuVax + Herceptin in TNBC, a population with a large unmet medical need.

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

About ESMO (Free ESMO Whitepaper)

The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) is Europe’s leading non-profit medical oncology organization. ESMO (Free ESMO Whitepaper) is a membership-based society, comprising of 500 expert committee members and 18,000 oncology professionals. ESMO (Free ESMO Whitepaper) organizes a large number of meetings to provide its members and the community with the resources they need and also plays a major role in public policy and European affairs. The ESMO (Free ESMO Whitepaper) 2018 Annual Meeting represents a multi-professional platform for oncology education and exchange, and for immense international visibility for scientific research, and will be held under the tagline "Securing access to optimal cancer care".

On July 22, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that its investigational BTK inhibitor zanubrutinib has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Waldenström macroglobulinemia (WM) (Press release, BeiGene, JUL 22, 2018, View Source;p=RssLanding&cat=news&id=2359338 [SID1234527801]). Based on BeiGene’s discussions with the FDA, internal review of available data from its global Phase 1 trial of zanubrutinib in patients with WM, and supported by the Fast Track Designation, BeiGene is preparing to submit in the first half of 2019 a New Drug Application (NDA) to pursue an accelerated approval of zanubrutinib for patients with WM based on results from the global Phase 1 study. A final determination to submit the NDA will be made subsequent to the pre-NDA meeting with FDA after obtaining mature data from the study this fall.

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"We believe zanubrutinib is a differentiated BTK inhibitor based on the depth and durability of responses observed in our ongoing global Phase 1 trial of zanubrutinib in WM patients. We look forward to working closely with the FDA in the continuing development of zanubrutinib for the treatment of this disease," commented John Oyler, co-founder, CEO and Chairman of BeiGene. "We are hopeful that zanubrutinib, if approved, may represent a valuable and important treatment option for patients with WM."

The FDA’s Fast Track program is intended to expedite or facilitate the process for reviewing new drugs that are intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and demonstrate the potential to address unmet medical needs for the condition. A drug candidate with a Fast Track Designation may be eligible for more frequent communications with the FDA, for Accelerated Approval and Priority Review (if relevant criteria are met), and rolling review of the NDA.

In addition to the global Phase 1 trial of zanubrutinib, which enrolled 76 WM patients to date, zanubrutinib is also being tested in a global Phase 3 clinical trial in patients with WM comparing zanubrutinib to ibrutinib, a currently approved BTK inhibitor. BeiGene announced today that this global Phase 3 study has completed patient enrollment. In addition, zanubrutinib is being tested in a global Phase 3 clinical trial as a first-line treatment for patients with chronic lymphocytic leukemia (CLL) and a Phase 2 clinical trial in patients with relapsed or refractory follicular lymphoma in combination with GAZYVA (obinutuzumab). In China, BeiGene has completed enrollment in three pivotal Phase 2 clinical trials of zanubrutinib in patients with mantle cell lymphoma (MCL), CLL and WM, and expects to file an NDA in China for MCL this year. BeiGene is also planning a Phase 3 trial for a head-to-head comparison of zanubrutinib versus ibrutinib in patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL). As of May 7, 2018, more than 1,200 patients have been enrolled in the zanubrutinib development program.

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various B cell malignancies.

On July 22, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that preliminary topline results from the independent review of response data from the pivotal Phase 2 trial of tislelizumab, an investigational anti-PD-1 antibody, in Chinese patients with relapsed/refractory classical Hodgkin’s lymphoma (R/R cHL) (Press release, BeiGene, JUL 22, 2018, View Source;p=RssLanding&cat=news&id=2359339 [SID1234527802]).

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"We are excited to announce the preliminary topline results from our first pivotal trial for tislelizumab. Despite short follow-up, we believe there was a demonstration of robust activity, with high overall and complete response rates in addition to a safety profile that is consistent with other PD-1 inhibitors. We believe these strong results will support our first regulatory filing in China for tislelizumab, which is planned for later this year," commented Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene.

The single-arm pivotal trial enrolled 70 patients with cHL who either failed autologous stem cell transplantation (ASCT) or who were ineligible for ASCT. The primary endpoint was overall response rate (ORR) as defined by the Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, time to response, safety, and tolerability. As of the data cutoff, the median follow-up time was approximately 6.0 months. A review of responses by an independent review committee, provided in June 2018, demonstrated:

The ORR was 73 percent, including 50 percent CR, and the median DOR had not been reached.

Frequency and severity of adverse events were generally consistent with the previously reported Phase 1 safety and tolerability data for tislelizumab, or, in the case of certain immune-related events such as hypothyroidism and fever, consistent with previous reports of other PD-1 antibodies for the treatment of cHL.
These cHL data, along with additional follow-up data from the clinical trial, are expected to be included in BeiGene’s Biologics License Application (BLA) planned to be filed with the China Drug Administration (CDA) later this year. Full results of the trial are expected to be presented at an upcoming medical conference.

Tislelizumab is also being studied in global Phase 3 trials in a number of malignancies, including non-small cell lung cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma; as well as two global Phase 2 trials in patients with previously treated hepatocellular carcinoma or with R/R mature T-and NK-cell lymphomas, and an additional pivotal Phase 2 trial in China in urothelial cancer.

About Classical Hodgkin’s Lymphoma
Classical Hodgkin’s lymphoma is one of the two major types of lymphoma that begin in the lymph nodes and tissues of the lymphatic system. All other lymphomas are classified as non-Hodgkin’s lymphomas. Hodgkin’s lymphoma is characterized by the presence of very large cells called Reed-Sternberg cells, although other abnormal cell types may be present. According to the Lymphoma Research Foundation, Hodgkin’s lymphoma is less common than non-Hodgkin’s lymphoma. There were approximately 2,100 diagnosed cases of Hodgkin’s lymphoma in China in 2012.1 Although the cancer can occur in both children and adults, it is most commonly diagnosed in young adults between the ages of 15 and 35 and in older adults over age 50.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).