On October 9, 2017 Clovis Oncology (NASDAQ: CLVS) reported that the company has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for rucaparib as maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy (Press release, Clovis Oncology, OCT 9, 2017, View Source [SID1234520815]). The sNDA submission is based on data from the phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied.

“The submission of the sNDA for rucaparib in the ovarian cancer maintenance setting just four months after we reported topline results marks an important milestone that brings Clovis closer to our ultimate goal of making rucaparib available to a broader population of women with advanced ovarian cancer,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We believe that the ARIEL3 results demonstrate the potential of rucaparib to provide a new, much-needed therapeutic option for women with advanced ovarian cancer.”

The phase 3 ARIEL3 clinical trial forms the basis of the rucaparib sNDA. ARIEL3 is a double-blind, placebo-controlled trial of rucaparib that enrolled 564 women with platinum-sensitive, high-grade ovarian, fallopian tube, or primary peritoneal cancer. The primary efficacy analysis evaluated three prospectively defined molecular sub-groups in a step-down manner: 1) BRCA mutant; 2) HRD-positive; and finally, 3) the intent-to-treat population, or all patients treated in ARIEL3.

Clovis announced positive topline results from the ARIEL3 clinical trial in June 2017. The comprehensive dataset from the trial was presented at the 2017 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Conference in Madrid, Spain,i and subsequently published in The Lancet.ii

Clovis intends to file a Marketing Authorization Application (MAA) in Europe in early 2018 for the maintenance indication, upon receipt of a potential approval in Europe for the ovarian cancer treatment indication.

About the ARIEL3 Clinical Trial

The ARIEL3 pivotal study of rucaparib is a confirmatory randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance treatment to platinum-sensitive ovarian cancer patients can extend the period of time for which the disease is controlled after a complete or partial response to platinum-based chemotherapy. The study enrolled 564 patients with high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer. To be eligible for the study, participants had to have received at least two prior platinum-based treatment regimens, been sensitive to the penultimate platinum regimen, and achieved a complete or partial response to their most recent platinum-based regimen. There were no genomic selection criteria for this study. Trial participants were randomized 2:1 to receive 600 milligrams of rucaparib twice daily (BID) or placebo.

About Rucaparib

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. In December 2016, rucaparib became the first PARP inhibitor approved by the U.S. Food and Drug Administration (FDA) as monotherapy for treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more prior chemotherapies. During the fourth quarter of 2016, the Marketing Authorization Application (MAA) submission in Europe for rucaparib in the same ovarian cancer treatment indication was submitted and accepted for review. In October 2017, Clovis Oncology submitted a supplemental New Drug Application (sNDA) in the U.S. for a second line or later maintenance treatment indication in ovarian cancer based on the ARIEL3 data, and in early 2018, plans to file an MAA in Europe for the maintenance treatment indication upon receipt of a potential approval for the treatment indication. Ongoing studies include the TRITON2 and TRITON3 (Trial of Rucaparib In Prostate Indications) studies in metastatic castration-resistant prostate cancer (mCRPC), the ARIEL4 (Assessment of Rucaparib in Ovarian Cancer Trial) confirmatory study in relapsed ovarian cancer patient with BRCA mutations, and the ATHENA (A Multicenter, Randomized, Double-Blind, Placebo-Controlled study of nivolumab and rucaparib Combination Switch Maintenance Following Front-Line Platinum-based Chemotherapy in Ovarian Cancer Patients) study is expected to begin before the end of 2017. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for rucaparib.

About Ovarian Cancer

According to the American Cancer Society, more than 22,400 women will be diagnosed with ovarian cancer in the U.S. in 2017. There are often no clearly identifiable initial symptoms, and in an estimated 80 to 85% of ovarian cancer cases, the cancer has spread to other parts of the body before a person is diagnosed and can be treated. Ovarian cancer ranks fifth in cancer deaths and causes more deaths than any other cancer of the female reproductive system.

On October 9, 2017 Bristol-Myers Squibb Company (NYSE: BMY) reported that it has appointed scientific and business thought-leader, Saurabh Saha, M.D., Ph.D., as senior vice president and global head of translational medicine in the company’s R&D organization, effective today (Press release, Bristol-Myers Squibb, OCT 9, 2017, View Source [SID1234520812]).

“Enhancing our translational medicine capability is critical to achieving our mission, and we are excited to add Dr. Saha’s broad leadership experience and deep scientific expertise to our team,” said Tom Lynch, M.D., executive vice president and chief scientific officer of Bristol-Myers Squibb. “Dr. Saha will lead translational research across our therapeutic areas of focus to ensure we have the best understanding of disease and asset-specific biology so we can deliver the right drug to the right patient at the right time.”

Dr. Saha said, “Throughout my career, I have had a passion for developing translational research strategies across disease areas, including oncology and immunology. I look forward to working with Tom and the rest of the R&D organization to advance Bristol-Myers Squibb’s industry-leading pipeline in a way that pushes the boundaries of science and enables us to rapidly deliver innovative medicines to patients with even greater precision.”

Dr. Saha will initially be based at the company’s Waltham, Mass research site until its new state-of-the-art research site in Cambridge, Mass opens in the fourth quarter of 2018.

About Dr. Saurabh Saha

Dr. Saha’s extensive research experience includes leading groundbreaking translational research and implementing innovative drug discovery strategies that have resulted in the discovery and development of two first-in-class cancer therapies and the pioneering of new approaches for unmet medical needs across therapeutic areas and clinical modalities.

Prior to joining Bristol-Myers Squibb, Dr. Saha was a venture partner at Atlas Venture where he held leadership positions with many of its portfolio biotech companies, including as chief medical officer of Synlogic, and as chief executive officer of Delinia until its sale to Celgene in early 2017. In 2008, Dr. Saha established the translational research and development organization BioMed Valley Discoveries where he served as chief scientific officer and later president, and was responsible for leading the development and demonstrating human effectiveness of novel cancer drugs for refractory and resistant disease, including an ERK inhibitor and a bacteriolytic immunotherapy. Earlier in his career, Dr. Saha was a consultant in the pharmaceutical practice at McKinsey and Company and subsequently appointed director and head of the New Indications Discovery Unit at Novartis. Dr. Saha is on the editorial boards of numerous prestigious medical journals and is an associate member and global clinical scholar at Harvard Medical School.

Dr. Saha holds an M.D. and Ph.D. in cancer genetics from The Johns Hopkins School of Medicine, where he completed his graduate studies in Bert Vogelstein’s lab. He is an alumnus of Harvard Business School and Oxford University, studying general management and biophysics respectively. Dr. Saha completed his undergraduate studies in biochemistry from the California Institute of Technology (Caltech).

On October 09, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported data presentations relating to its technology platforms to be given at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 32ND Annual Meeting taking place in National Harbor, Maryland, November 8-12, 2017 (Press release, Aduro Biotech, OCT 9, 2017, View Source [SID1234520811]).

Poster 335: Characterization of a novel differentiated anti-CTLA-4 antibody (ADU-1604) in vitro and in vivo
Date/Time: Friday, November 10, 12:30 p.m. to 2:00 p.m. EST
Poster Hall Location: Prince George’s Exhibition Hall DE

Poster 61: Cellular and genomic disease signature of peripheral blood mononuclear cells in patients with malignant pleural mesothelioma
Date/Time: Friday, November 10, 12:30 p.m. to 2:00 p.m. EST
Poster Hall Location: Prince George’s Exhibition Hall DE

Poster 133: A heterologous prime-boost vaccination strategy combining a Listeria and DNA-based vaccine encoding prostatic acid phosphatase (PAP) elicits a strong antigen-specific, anti-tumor response
Date/Time: Friday, November 10, 12:30 p.m. to 2:00 p.m. EST
Poster Hall Location: Prince George’s Exhibition Hall DE
Per SITC (Free SITC Whitepaper) guidelines, abstracts are embargoed until 8:00 a.m. EST on November 7, 2017. To view abstracts, please visit the SITC (Free SITC Whitepaper) website at View Source

On October 9, 2017 AstraZeneca, along with MedImmune, its global biologics research and development arm, reported that the European Medicines Agency (EMA) has accepted a Marketing Authorisation Application (MAA) for Imfinzi (durvalumab) for the treatment of patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy (Press release, AstraZeneca, OCT 9, 2017, View Source [SID1234520810]). This is the first registrational submission for Imfinzi in the European Union.

The MAA submission acceptance is an important milestone for Imfinzi in a disease state where patients need better treatment options and outcomes. Currently, the standard of care for patients with this earlier stage of lung disease is active monitoring following concurrent chemoradiation.

The MAA submission is based on positive progression-free survival (PFS) data from the Phase III PACIFIC trial. The trial continues to evaluate overall survival (OS), its other primary endpoint. Detailed results of the PACIFIC trial, including additional safety information, were published online in the New England Journal of Medicine.

NOTES TO EDITORS

About Locally-Advanced (Stage III) NSCLC

Locally-advanced (Stage III) lung cancer is commonly divided into two stages (IIIA and IIIB), which are 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 lung cancer represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-7 countries in 2016[1]. More than 70% of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.

The trial is being conducted in 235 centres across 26 countries involving approximately 700 patients. The primary endpoints of the trial are progression-free survival (PFS) and overall survival (OS), and secondary endpoints include landmark PFS and OS, objective response rate (ORR) and duration of response.

About Imfinzi

Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response.

Imfinzi has already received accelerated approval in the US for the treatment of patients with locally advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

As part of a broad development programme, Imfinzi is also being investigated for the adjuvant treatment of patients with NSCLC in the CCTG (Canadian Cancer Trials Group) trial ADJUVANT (BR31). In the MYSTIC, NEPTUNE, and PEARL Phase III trials, Imfinzi is being studied for 1st-line treatment as monotherapy and/or in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody, for the treatment of metastatic NSCLC. The POSEIDON trial is investigating Imfinzi with and without tremelimumab in combination with chemotherapy in the same population.

On October 9, 2017 AstraZeneca reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for Tagrisso (osimertinib) for the 1st-line treatment of patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, OCT 9, 2017, View Source [SID1234520809]).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The Breakthrough Therapy Designation acknowledges not only Tagrisso’s potential as a 1st-line standard of care in advanced EGFR mutation-positive NSCLC, but also the significant need for improved clinical outcomes in this disease. The results of the FLAURA trial have the potential to redefine clinical expectations and offer new hope for patients who currently have a poor prognosis.”

The FDA granted the BTD based on data from the Phase III FLAURA trial of Tagrisso versus standard-of-care EGFR tyrosine kinase inhibitor (TKI) therapy in previously-untreated patients with locally-advanced or metastatic EGFR mutation-positive NSCLC. In the trial, median progression-free survival was nearly double at 18.9 months for Tagrisso compared with 10.2 months for current 1st-line EGFR TKIs (erlotinib or gefitinib). Improvements were seen in all pre-specified subgroups, including patients with and without brain metastases. Tagrisso was well tolerated with a safety profile consistent with previous experience.

On 28 September 2017, the US National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology were updated to include the use of Tagrisso in the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC. The use of Tagrisso for the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC is not yet FDA approved. However, Tagrisso is currently approved in more than 50 countries, including the US, EU, Japan and China, as 2nd-line treatment for patients with advanced NSCLC who progress following treatment with an EGFR TKI due to the EGFR T790M resistance mutation.

This is the sixth BTD that AstraZeneca has received from the FDA for an oncology medicine since 2014. BTD is designed to expedite the development and regulatory review of new medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which demonstrate substantial improvement on a clinically-significant endpoint over available medicines and when there is significant unmet medical need.

About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFR-mutated NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to EGFR TKI treatment leading to disease progression. Approximately half of patients develop resistance to approved EGFR TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M. Tagrisso also targets this secondary mutation that leads to disease progression. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFR-mutated NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against central nervous system (CNS) metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in more than 50 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

About FLAURA

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg once daily vs standard-of-care EGFR TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFR-mutated NSCLC. The trial was a double-blinded, randomised study, with 556 patients across 30 countries.

The primary endpoint of the trial was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), safety, and measures of health-related quality of life (HRQoL).