On October 9, 2017 ARMO BioSciences, Inc., a late-stage immuno-oncology company, reported the appointment of Joseph Leveque, M.D. as Chief Medical Officer. An accomplished industry veteran, Dr. Leveque has significant experience in immuno-oncology drug development, with a focus on bringing novel therapies to patients living with cancer (Press release, ARMO BioSciences, OCT 9, 2017, View Source [SID1234520853]).

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Dr. Leveque will lead the ongoing and planned pivotal Phase 3 clinical trials of ARMO’s lead investigational immuno-oncology drug AM0010 (pegilodecakin, PEGylated Interleukin-10) as well as the plans to advance the Company’s pipeline, which includes an anti-PD-1 monoclonal antibody.

"Joe has been on the forefront of innovation in the immuno-oncology field and has successfully brought multiple drugs to patients," said Peter Van Vlasselaer, Ph.D., President and Chief Executive Officer of ARMO BioSciences. "After being involved in developing some of the most important breakthrough immuno-oncology drugs, Joe brings valuable experience to the company as we advance AM0010, which we believe may offer the next important breakthrough in this field. We are confident that Joe will help drive the full potential of this novel cancer therapy as well as our broader pipeline."

"Over the past decade, I was involved in the development and commercialization of the first generation of immuno-oncology (IO) therapeutics, including a CTLA-4 inhibitor, a PD-1 inhibitor, and a PD-L1 inhibitor," said Dr. Leveque. "I believe next-generation IO therapeutics like AM0010, used alone or in combination with other IO therapies or other novel approaches, have the promise to significantly advance the oncology field and provide renewed hope to cancer patients who have difficult-to-treat tumors."

Dr. Leveque has more than 20 years of experience in the biopharmaceutical industry leading teams in the successful development and commercialization of oncology therapeutics. Dr. Leveque was the Chief Medical Officer of EMD Serono, the North America subsidiary of Merck KGaA and the Vice President and Head of U.S. Medical Oncology at Bristol-Myers Squibb (BMS) where he was involved in the development and commercialization of the first generation of immuno-oncology (IO) therapeutics, including Bavencio, Opdivo and Yervoy. Prior to BMS, Dr. Leveque was the Vice President of Medical and Scientific Affairs at Onyx Pharmaceuticals, where he was involved in the development of Kyprolis and was recognized by the Multiple Myeloma Research Foundation as one of the top 15 innovators in multiple myeloma over the last 15 years. Earlier in his career, he served as Vice President of Medical and Scientific Affairs at Cephalon Oncology and a Medical Director at Amgen, where he worked on several therapeutic programs for solid tumor and hematological malignancies.

Dr. Leveque received a Bachelor of Arts and Sciences with an emphasis in biology from the Santa Clara University. He earned a Medical Doctorate from University of Texas School of Medicine in Houston and completed his post-graduate medical training in internal medicine at the Cedars-Sinai Medical Center, a teaching affiliate of UCLA. In addition, Dr. Leveque holds a Master in Business Administration from the Wharton School of the University of Pennsylvania.

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;p=RssLanding&cat=news&id=2305489 [SID1234520821]). 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.

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"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 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 [SID1234520816]).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The Breakthrough 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 osimertinib 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 18.9 months for osimertinib compared with 10.2 months for EGFR-TKIs (erlotinib or gefitinib). Improvements were seen in all pre-specified subgroups, including patients with and without brain metastases.

In the FLAURA trial, the safety profile of osimertinib was consistent with previous experience. In patients treated with osimertinib, the most common AEs were diarrhea (58%, any grade [2% Grade ≥3]) and dry skin (32%, any grade [<1% Grade ≥3]), and in the comparator arm group the most common AEs were diarrhea (57%, any grade [2% Grade ≥3]) and dermatitis acneiform (48%, any grade [5% Grade ≥3]). Of the patients on osimertinib, 34% had a Grade ≥3 AE, compared to 45% in the comparator arm, and 13% of patients on osimertinib had an AE leading to treatment discontinuation compared to 18% in the comparator arm.

On September 28, 2017, the US NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) were updated to include the use of osimertinib in the 1st-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC. The use of osimertinib for the first-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC is not yet FDA approved.

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. TAGRISSO once-daily tablets are approved by the FDA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy. TAGRISSO is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M 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.

TAGRISSO (osimertinib) Important Safety Information

There are no contraindications for TAGRISSO
Interstitial Lung Disease (ILD)/Pneumonitis occurred in 3.5% and was fatal in 0.6% of 833 TAGRISSO-treated patients. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD is confirmed
Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 833 TAGRISSO-treated patients, 0.7% of patients were found to have a QTc > 500 msec, and 2.9% of patients had an increase from baseline QTc > 60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
Cardiomyopathy occurred in 1.9% and was fatal in 0.1% of 833 TAGRISSO-treated patients. Left Ventricular Ejection Fraction (LVEF) decline ≥ 10% and a drop to < 50% occurred in 4% of 655 TAGRISSO-treated patients. Conduct cardiac monitoring, including an assessment of LVEF at baseline and during treatment in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue TAGRISSO
Keratitis was reported in 0.7% of 833 TAGRISSO-treated patients in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye) to an ophthalmologist
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during TAGRISSO treatment and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
The most common adverse reactions (≥20%) in patients treated with TAGRISSO were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%)
Please see complete Prescribing Information including Patient Information.

NOTES TO EDITORS

About Non-Small Cell Lung Cancer (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% to 15% of patients in the US and Europe, and 30% to 40% of patients in Asia have epidermal growth factor receptor mutation-positive (EGFRm) NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR tyrosine kinase inhibitors (TKIs), which block the cell signaling pathways that drive the growth of tumor cells. However, tumors 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 targets this secondary mutation that leads to disease progression. There is also a need for agents with improved central nervous system efficacy since approximately 25% of patients with EGFRm NSCLC have brain metastases at first diagnosis, increasing to approximately 40% within two years of diagnosis.

About TAGRISSO (osimertinib)
TAGRISSO (osimertinib) is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to inhibit both EGFR sensitizing 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 non-small cell lung cancer. Eligibility for treatment with TAGRISSO is dependent on confirmation that the EGFR T790M mutation is present in the tumor.

TAGRISSO is also being investigated in the adjuvant and metastatic 1st-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases and in combination with other treatments.

About FLAURA
FLAURA assessed the efficacy and safety of osimertinib 80mg orally once daily vs. standard-of-care epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously untreated patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer. The trial was a double-blinded, randomized study, with 556 patients across 30 countries.

The primary endpoint of the trial was progression-free survival, and secondary endpoints included overall survival, objective response rate, duration of response, disease control rate, safety and measures of health-related quality of life.