On June 27, 2019 AstraZeneca reported positive overall survival (OS) results from the Phase III CASPIAN trial with Imfinzi in 1st-line extensive-stage small cell lung cancer (SCLC), a disease with significant unmet need and limited treatment options for patients (Press release, AstraZeneca, JUN 27, 2019, View Source [SID1234537295]).

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A planned interim analysis conducted by an Independent Data Monitoring Committee concluded that the trial has met its primary endpoint by showing a statistically-significant and clinically-meaningful improvement in OS in patients treated with Imfinzi in combination with standard-of-care etoposide and platinum-based chemotherapy options vs. chemotherapy alone. The safety and tolerability for this Imfinzi combination was consistent with the known safety profiles of these medicines.

AstraZeneca will submit these results for presentation at a forthcoming medical meeting.

José Baselga, Executive Vice President, Oncology R&D said: "The Phase III CASPIAN results offer new hope for patients who are facing the devastating diagnosis of small cell lung cancer, and for whom new medicines are urgently needed. This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options."

CASPIAN is a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy options or the combination of Imfinzi, tremelimumab and chemotherapy vs. chemotherapy alone as a 1st-line treatment for patients with extensive-stage SCLC. The trial will continue to the final analysis of OS for the combination of dual immune checkpoint blockade with chemotherapy. This combination includes tremelimumab, an anti-CTLA4 antibody and potential new medicine, with Imfinzi, an anti-PDL1 antibody, and chemotherapy.

Imfinzi is also being tested following concurrent chemoradiation therapy in limited-stage SCLC in the Phase III ADRIATIC trial.

Imfinzi is approved for unresectable, Stage III non-small cell lung cancer in more than 45 countries, including the US, EU and Japan, based on the Phase III PACIFIC trial.

About CASPIAN

The CASPIAN trial is a randomised, open-label, multi-centre, global, Phase III trial in the 1st-line treatment of patients with extensive-stage SCLC. The trial compared Imfinzi in combination with etoposide and either cisplatin or carboplatin chemotherapy, or Imfinzi, tremelimumab and chemotherapy vs. chemotherapy alone. In the experimental arms, patients were treated with up to four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and prophylactic cranial irradiation.

The trial is being conducted in more than 200 centres across 22 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint is OS.

About small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.2 About two-thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.3 SCLC is an aggressive, fast-growing cancer that recurs and progresses rapidly despite initial response to platinum-based chemotherapy.4 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.3

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.

Imfinzi is also approved for previously-treated patients with advanced bladder cancer in the US, Canada, Brazil, Australia, Israel, India, United Arab Emirates, Qatar, Macau and Hong Kong.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.

About tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, bladder cancer, head and neck cancer, liver cancer and blood cancers.

About AstraZeneca in lung cancer

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 spanning several stages of disease, lines of therapy and modes of action. 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 (gefitinib) and Tagrisso (osimertinib) and ongoing Phase III trials FLAURA, ADAURA and LAURA as well as the Phase II exploratory combination trials SAVANNAH and ORCHARD.5-7

Our extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a known genetic mutation which represents up to 50% of all patients with lung cancer. Imfinzi (durvalumab), an anti-PDL1 antibody, is in development as monotherapy (Phase III trials ADJUVANT BR.31, PACIFIC-4, PACIFIC-5, and PEARL) and in combination with tremelimumab and/or chemotherapy (AEGEAN, PACIFIC-2, NEPTUNE, POSEIDON, ADRIATIC and CASPIAN Phase III trials).

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

IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. Our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies 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 from 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 advance Oncology as a key 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 June 27, 2019 Calithera Biosciences reported that Cancer cells are known to rely on glycolysis as an energy source (Press release, Calithera Biosciences, JUN 27, 2019, View Source [SID1234537318]). CB-839 (Calithera Biosciences) inhibits the glutaminase enzyme, reducing the ability of cancer cells to utilize glutamine in this biochemical pathway, thereby reducing cell proliferation and tumor growth.

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If approved, CB-839 will be the first glutaminase inhibitor approved for the treatment of renal cell carcinoma (RCC). This novel mechanism of action could place CB-839 in a unique position in the RCC market and provide physicians with an alternative treatment option.

CB-839 is being investigated in combination with either Afinitor (everolimus; Novartis) or Cabometyx (cabozantinib; Exelixis/Ipsen/Takeda) for previously treated advanced RCC patients, suggesting it will not compete with the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) therapies being developed for first-line use.

CB-839 is being developed by Calithera Biosciences, a company that is yet to bring an oncology product to market. Due to Calithera’s limited geographic scope, the author expects the company to look for partners to market CB-839 in Japan and the EU.

Key Topics Covered:

OVERVIEW

Drug Overview
Product Profiles
CB-839 : Renal cell carcinoma (RCC)
LIST OF FIGURES

CB-839 for RCC – SWOT analysis
The authors drug assessment summary of CB-839 for RCC
CB-839 sales for RCC in the US, 2017-26
LIST OF TABLES

CB-839 drug profile
CB-839 Phase II trials in RCC
CB-839 sales for RCC in the US ($m), 2017-26
For more information about this report visit View Source

On June 24, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), reported that Adrian Rawcliffe, currently Chief Financial Officer (CFO) of the Company, will succeed James Noble as Chief Executive Officer (CEO) (Press release, Adaptimmune, JUN 27, 2019, View Source [SID1234537319]). This transition will occur when James retires from his executive duties and transitions to a non-executive director role on the Company’s Board on September 1, 2019. Adrian will join the Board of Directors from the same date.

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"Following James’ request early last year, the Board has been planning for leadership succession. Today, I am pleased to announce Adrian’s appointment, following a rigorous global selection process," said David Mott, Adaptimmune’s Chairman of the Board. "We were very fortunate to have Adrian as a candidate, not only given his role as CFO, covering a wide range of responsibilities from manufacturing to information management, but also his previous experiences at GSK. I want to thank James for his leadership, energy and drive, which has delivered the Company’s science, current pipeline, manufacturing expertise, and strong teams. Based on these strengths, Adrian will now lead the Company towards commercialization."

"I am delighted and privileged to have been chosen to succeed James as CEO. Since I joined Adaptimmune, I have been intimately involved in building the Company working alongside the Executive Committee and the Board. The opportunity for cell therapy to transform the lives of cancer patients is profound. Over the next two months, I will work with James and the other Company leaders to ensure a smooth handover. I am excited about the future and look forward to delivering rapidly the promises of our investigational therapies, focussing on SPEARHEAD-1, our next-gen trial, and advancing our allogeneic platform" said Adrian Rawcliffe.

James Noble said: "Over the past 20 years leading Adaptimmune and its predecessor company Avidex, I am proud to have built technologies, teams and partnerships to create strong R&D platforms and a rich pipeline. Now that the Company is about to start SPEARHEAD-1 and our first next-gen trial, it is the right time to hand over the CEO role to someone to lead Adaptimmune’s next phase towards delivering our first approved product to patients. Having worked with Adrian over the past four and a half years, I have confidence that he is the best person to do this. I look forward to continuing being involved in the next steps of the Company’s journey, as a non-executive Board member."

The Company has started a global search for a new CFO, which will be the subject of a separate announcement.

Since he joined Adaptimmune as Chief Financial Officer in March 2015, Adrian has led the Company’s financial strategy and operations, as well as investor relations, corporate communications, manufacturing and supply chain, product development, information management and facilities. He currently serves as a non-executive director of WAVE Life Sciences (NASDAQ: WVE). Before joining Adaptimmune, he held various senior roles at GSK, after joining the pharmaceutical company in 1988. His most recent role at GSK was Senior Vice President, Finance of the North American Pharmaceuticals business. Other roles at GSK included Senior Vice President Worldwide Business Development and R&D Finance, where he was responsible for all business development and finance activities for GSK’s Pharmaceuticals R&D business and Managing Partner and President of SR One Ltd, GSK’s venture-capital business. Adrian qualified as a chartered accountant with PwC and holds a B.Sc. degree in Natural Sciences from the University of Durham, U.K.

After co-founding the Company, James Noble has served as Adaptimmune’s full-time Chief Executive Officer since March 2014, and part-time CEO from July 2008 to March 2014. During the same period, between July 2008 and March 2014, Mr. Noble was also CEO of Immunocore. He has 30 years of experience in the biotech industry. He has held numerous non-executive director positions, including at CuraGen Corporation, PowderJect Pharmaceuticals plc, Oxford GlycoSciences plc, MediGene AG, and Advanced Medical Solutions plc. He is also Deputy Chairman of GW Pharmaceuticals plc (NASDAQ: GWPH). He qualified as a chartered accountant with Price Waterhouse and spent seven years at the investment bank Kleinwort Benson Limited, where he became a director in 1990. He then joined British Biotech plc as Chief Financial Officer from 1990 to 1997. He was previously Chief Executive Officer of Avidex Limited, a privately held biotechnology company that was Adaptimmune’s predecessor, from 2000 to 2006. He holds an M.A. from the University of Oxford.

On June 27, 2019 ArQule, Inc. (Nasdaq: ARQL) reported the closing of its previously announced underwritten public offering of common stock, including the exercise in full by the underwriters of their option to purchase an additional 1,387,500 shares at the public offering price of $9.75 per share (Press release, ArQule, JUN 27, 2019, View Source [SID1234537297]). The exercise of the option to purchase additional shares brought the total number of shares of common stock sold by ArQule to 10,637,500 shares and increased the gross proceeds raised in the offering, before deducting underwriting discounts and commissions and estimated expenses of the offering payable by ArQule, to approximately $103.7 million.

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The Company intends to use the net proceeds of the offering to fund its clinical programs and for general corporate purposes.

SVB Leerink and RBC Capital Markets acted as joint bookrunning managers for the offering. Oppenheimer & Co. Inc. and Needham & Company acted as co-lead managers, and Roth Capital Partners, B. Riley FBR and JonesTrading Institutional Services LLC acted as co-managers for the offering.

The securities described above were offered by ArQule pursuant to an effective shelf registration statement on Form S-3 (File. No. 333-232306), including a base prospectus, that was filed by ArQule with the Securities and Exchange Commission ("SEC") and automatically became effective on June 24, 2019. A final prospectus supplement and accompanying prospectus relating to the offering filed with the SEC is available on the SEC’s website located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132, or by email at [email protected]; or from RBC Capital Markets, LLC, Attention: Equity Syndicate, 200 Vesey Street, 8th Floor, New York, NY 10281, by telephone at (877) 822-4089.

This press release does not constitute an offer to sell or a solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

On June 27, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the U.S. Food and Drug Administration (U.S. FDA) has approved the use of DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) (Press release, Genmab, JUN 27, 2019, View Source [SID1234537320]). The supplemental Biologics License Application (sBLA) for this indication was submitted by Genmab’s licensing partner, Janssen Biotech, Inc., under the Real-Time Oncology Review (RTOR) pilot program. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"The combination of lenalidomide and dexamethasone is broadly used by newly diagnosed patients with multiple myeloma ineligible for ASCT in the United States. We are extremely pleased that physicians can now offer their patients the option to add DARZALEX to this regimen in the U.S.," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval was based on data from the Phase III MAIA (MMY3008) study of daratumumab in combination with lenalidomide and dexamethasone as treatment for patients with newly diagnosed multiple myeloma, who are not candidates for high dose chemotherapy and ASCT. Data from this study was presented as a Late-Breaking Abstract at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.

About the MAIA (MMY3008) study
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high dose chemotherapy and ASCT. Patients were randomized to receive either daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide was administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone was administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue treatment with lenalidomide and dexamethasone until disease progression or unacceptable toxicity. The primary endpoint of the study is progression free survival.

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 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 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

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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.6 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 in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. 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).6,7,8,9,10

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, 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.