On September 24, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) recording that updated phase 1 safety and efficacy data for [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), were presented for a subgroup of patients with heavily pretreated HER2 mutated or HER2 expressing non-small cell lung cancer (NSCLC) during an Oral Session at the IASLC 19th World Conference on Lung Cancer (#WCLC2018) hosted by the International Association for the Study of Lung Cancer in Toronto, Canada (Press release, Daiichi Sankyo, SEP 24, 2018, View Source [SID1234529547]).

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An updated subgroup analysis of 11 patients with HER2 mutated NSCLC receiving a recommended expansion dose of 6.4 mg/kg showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 72.7 percent (8 of 11 patients) and disease control rate of 100 percent (11 of 11 patients). Preliminary estimate of median duration of response has reached 11.5 months (95 percent CI: 0.03+, 11.5) and median progression-free survival has reached 14.1 months (95 percent CI: 4.0+, 14.1) for this subgroup of patients.

"These preliminary results seen with [fam-] trastuzumab deruxtecan are encouraging, particularly given the existing unmet medical need for patients with metastatic NSCLC with HER2 alterations that have progressed on several prior therapies," said Junji Tsurutani, MD, PhD, Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan, a study investigator. "These results also demonstrate that continued evaluation of treatments that target the HER2 receptor is warranted in patients with NSCLC."

The updated subgroup analysis of 17 patients with heavily pretreated HER2 mutated or HER2 expressing (defined as IHC ≥1+ or amplified) NSCLC showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 58.8 percent (10 of 17 patients) and a disease control rate of 88.2 percent (15 of 17 patients). Preliminary estimate of median duration of response has reached 9.9 months (95 percent CI: 0.0+, 11.5) and median progression-free survival has reached 14.1 months (95 percent CI: 0.9, 14.1).

"Patient enrollment is currently underway into our phase 2 study of [fam-] trastuzumab deruxtecan in patients with advanced HER2 mutated or HER2 overexpressing NSCLC," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "Since there are no therapies specifically approved to treat patients with HER2 altered NSCLC, continued study of [fam-] trastuzumab deruxtecan is needed to better understand the potential role of a HER2 targeting antibody drug conjugate in treating these patients."

Updated preliminary safety data for this subgroup of patients with heavily pretreated HER2 mutated or HER2 expressing NSCLC receiving [fam-] trastuzumab deruxtecan were also reported. The most common adverse events (>30 percent, any grade) included nausea (50.0 percent), decreased appetite (50.0 percent), alopecia (50.0 percent), fatigue (44.4 percent) and vomiting (38.9 percent). Grade 3 adverse events occurring in >10 percent of patients included decreased neutrophil count (11.1 percent). As previously reported, one (1) grade 5 event of pneumonitis was observed in this cohort, which was adjudicated as unrelated to [fam-] trastuzumab deruxtecan by an independent adjudication committee. Any reported cases of interstitial lung disease (ILD)/pneumonitis in the [fam-] trastuzumab deruxtecan clinical development program are evaluated by an independent adjudication committee.

Unmet Need in Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the most common cancer in the world and the leading cause of cancer deaths.1 There were approximately 1.8 million new cases of lung cancer reported globally and approximately 1.6 million deaths in 2012.1 Non-small cell lung cancer (NSCLC) accounts for approximately 80 to 85 percent of all cases.2 The five-year survival rate for metastatic NSCLC is only one percent.3

The introduction of targeted therapies and checkpoint inhibitors in recent years has improved the treatment landscape for metastatic NSCLC patients, who previously had limited options beyond systemic chemotherapy.4,5 However, for those who are not eligible for available treatments, or whose cancer continues to progress, new approaches are needed to help manage the disease.6

HER2 overexpression has been reported in rates ranging from 4 to 35 percent of NSCLC, depending on the published series and methods, and is associated with poor disease prognosis and shortened overall survival.4,6 HER2 mutations have more recently been identified as distinct molecular targets for NSCLC and have been reported in up to 5 percent of NSCLC.7,8 Currently, no therapy is specifically approved for HER2 mutated or HER2 overexpressing non-small cell lung cancer.

About the [Fam-] Trastuzumab Deruxtecan Phase 1 Study

An open-label, two-part phase 1 study is currently evaluating [fam-] trastuzumab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of this study was to assess the safety and tolerability of and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.9

In the dose expansion part of the phase 1 study, [fam-] trastuzumab deruxtecan is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2 positive advanced or metastatic breast cancer and gastric cancer, HER2 low expressing breast cancer and other HER2 expressing solid tumors including NSCLC. Overall, 292 patients have been enrolled into this phase 1 study of [fam-] trastuzumab deruxtecan. For more information about the study, visit ClinicalTrials.gov.

About [Fam-] Trastuzumab Deruxtecan

[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to ado-trastuzumab emtansine (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: [fam-] trastuzumab deruxtecan, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory FLT3-ITD acute myeloid leukemia (AML); and pexidartinib, an oral CSF1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com.

On September 24, 2018 Bausch Health Companies Inc. (NYSE/TSX: BHC) reported that the company will participate in two investor conferences in October (Press release, Valeant, SEP 24, 2018, View Source [SID1234529771]).

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Joseph C. Papa, chairman and chief executive officer, and Sam Eldessouky, senior vice president and corporate controller, are scheduled to participate at the Cantor Fitzgerald Global Healthcare Conference in New York on Oct. 1, 2018 at 3:30 p.m. EDT.

Paul S. Herendeen, executive vice president and chief financial officer, William Woodfield, vice president and treasurer, and Arthur J. Shannon, senior vice president and head of Investor Relations and Communications, are scheduled to participate at the Deutsche Bank 26th Annual Leveraged Finance Conference in Scottsdale, Ariz. on Oct. 2, 2018 at 10:40 a.m. MST (1:40 p.m. EDT).

Live webcasts and audio archives of the events will be available on the Investor Relations page of the Bausch Health Companies Inc. web site at: View Source

On September 24, 2018 Transgene (Paris:TNG) (Euronext Paris: TNG) a biotechnology company that designs and develops virus-based immunotherapies against cancers and infectious diseases, reported myvacTM, an individualized, viral vector-based immunotherapy against cancer that will enter clinical development in 2019 (Press release, Transgene, SEP 24, 2018, View Source [SID1234621824]).

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myvacTM, an individualized, MVA-based immunotherapy
myvacTM is designed to stimulate and educate the immune system of patients to recognize and destroy tumor cells. The personalized immunotherapy product is based on the mutations that are identified in the patient’s own tumor. These mutations are highly relevant targets since they lead to the expression of tumor neoantigens which are known to trigger a stronger immune response than "classic"2 tumor antigens.

Once administered to the patient, myvacTM triggers a cascade of immune responses against a variety of targets found in the cancer cells.

The neoantigens which are the basis for the myvacTM approach are identified by sequencing and selected using artificial intelligence algorithms, and then integrated into the genome of the viral vector (MVA).

myvacTM differs from autologous treatments since no biological material from the patient is used in the manufacturing process and as such is much easier to manufacture; it is a truly individualized approach that uses the information that is specific to the characteristics of each patient’s tumor.

Transgene has combined its expertise in viral vectors with highly innovative technologies to develop myvacTM.

myvacTM features several key advantages:

It is expected to deliver the benefits of an individualized treatment without the disadvantages of autologous approaches (Transgene does not modify the patient’s cells but integrates the neoantigen panel into the virus);
It is based on a viral strain (MVA) whose safety, tolerability, immunogenicity and efficacy have already been demonstrated in the clinic with TG4010 and TG4001;
The myvacTM viral vector (MVA) has repeatedly shown that it can induce a strong immune response from the patient against the tumor antigens incorporated in its viral genome as well as an enlargement of the antitumoral immune repertoire (epitope spreading);
An "all-in-one" formula, requiring neither adjuvant nor association of different peptides.
Éric Quéméneur, PhD, Executive VP, Chief Scientific Officer of Transgene, said: "With myvacTM, Transgene is at the forefront of innovation in cancer immunotherapy. Based on our know-how in virotherapy, we have successfully integrated sequences coding for neoantigens to create an individualized immunotherapy. By combining sequencing and artificial intelligence with the design of the virus, myvacTM marks the entry of viral vector-based approaches in the era of digital transformation. Importantly we have also set up an organization able to design and manufacture myvacTM for each patient in a timely and cost-competitive manner. The myvacTM innovation is a logical evolution of our expertise and a new therapeutic option that promises a major improvement over existing therapies. myvacTM is also the result of our policy of open innovation which is based on working with partners developing technologies that are complementary to our expertise allowing us to benefit from a multidisciplinary approach. We look forward to demonstrating the transformative potential of myvacTM in the clinical trials we plan to start in 2019."

myvacTM, an ambitious project expected to enter the clinic in 2019
myvacTM will be administered to patients with solid tumors. Two clinical trials are being set up in Europe and in the United States, including HPV-negative head and neck cancers and ovarian cancer. These trials are expected to start in 2019.
The first preclinical and translational results will be presented soon at immuno-oncology conferences.

Our innovative network combines bioengineering and digital transformation

To design myvacTM, Transgene and its collaborative network had to overcome many scientific and technical challenges. The network’s expertise covers all the required know-how:

Institut Curie (Cancer Immunotherapy Center, led by Professor Amigorena) is involved in the generation of translational data and the characterization of the mechanism of action;
HalioDx studies biomarkers to maximize the effectiveness of the therapy;
Traaser automates, secures and manages genomic data, including predictive algorithms provided by a recognized partner in artificial intelligence;
Transgene has developed a unique manufacturing pilot unit in France to vectorize neoantigens and provide myvacTM within a timeframe compatible with clinical treatment schemes.
This innovative project has obtained the labeling of the Biovalley France and Eurobiomed French competitiveness clusters.

Transgene holds the intellectual property of the myvacTM viral vector platform and is actively working on the translational development of this innovative technology.

On September 24, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion to expand the indication for Xtandi (enzalutamide) to include adult men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Astellas, SEP 24, 2018, View Source [SID1234529658]).2 If approved by the European Commission (EC), enzalutamide will be one of the first treatments approved for this critical stage of disease, currently associated with a significant unmet medical need. Enzalutamide was first approved by the EC in June 2013 and is currently indicated in the treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT) in whom chemotherapy is not yet clinically indicated or whose disease has progressed on or after docetaxel therapy.3

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"In nmCRPC, the high risk patient is at a stage where his cancer is growing even though it’s not visible yet despite hormone therapy and will manifest itself given time. The objective of early access to enzalutamide in these patients is to delay the emergence of metastasis with the hope of improving quantity and quality of life," said Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, United States, and lead study investigator. "The potential of an effective treatment option for this stage of disease signifies an important therapeutic advancement."

The CHMP opinion is based on the results from the pivotal phase 3 PROSPER trial which evaluated enzalutamide plus ADT vs placebo plus ADT in patients with nmCRPC and rapidly rising prostate-specific antigen (PSA) levels.1 The trial met its primary endpoint of metastasis-free survival (MFS). The median MFS was 36.6 months for men who received enzalutamide plus ADT, compared to 14.7 months with placebo plus ADT (n=1401; HR=0.29 [95% CI: 0.24–0.35]; p<0.001).1

The PROSPER trial results indicated a 71% reduction in the risk of radiographic progression or death in men with nmCRPC and rapidly rising PSA levels, compared to placebo plus ADT (HR=0.29 [95% CI: 0.24–0.35]; p<0.001).1 The most common adverse events of any grade for patients ≥10% and higher for enzalutamide plus ADT vs placebo plus ADT were: fatigue (33% vs 14%), hot flush (13% vs 8%), hypertension (12% vs 5%), nausea (11% vs 9%), fall (11% vs 4%), dizziness (10% vs 4%) and decreased appetite (10% vs 4%).1 These results were published in the June 2018 edition of the New England Journal of Medicine.1

"This positive CHMP opinion represents an important step towards providing specialist health care professionals with a new treatment option for patients with nmCRPC and rapidly rising levels of prostate specific antigen. These patients are at higher risk of developing metastasis and death. Subject to EMA approval, we have the potential to expand the use of enzalutamide in a patient population where there is a clear unmet medical need," said Steven Benner, M.D, Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas.

The positive opinion from the CHMP will now be reviewed by the EC, which has the authority to approve medicines for the 28 European Union member countries plus Iceland, Norway and Liechtenstein. The EC, which generally follows the recommendation of the CHMP, is expected to make its final decision in the final quarter of 2018.

PROSPER Trial Results
PROSPER is a double-blind, placebo-controlled, pivotal phase 3 trial conducted at 300 sites in 32 countries that randomised 1,401 patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and a prostate-specific antigen (PSA) doubling time of 10 months or less, 2:1 to either receive once-daily enzalutamide plus androgen deprivation hormone therapy (ADT) (n=933) or placebo plus ADT (ADT alone [n=468]), respectively.1

Secondary outcomes included a statistically significant delay in the median time to first use of new antineoplastic therapy (TTA) of 39.6 vs 17.7 months; HR=0.21 [95% CI: 0.17–0.26]; p<0.001 for patients who received enzalutamide plus ADT compared to those who received placebo plus ADT.1

About Prostate Cancer
Prostate cancer is the most common cancer diagnosis for men in the European Union (EU).4 There are 375,842 men in the EU currently diagnosed with prostate cancer, accounting for an estimated 23.2% of all cancers in men in 2018.4 Some studies estimate that, within five years of diagnosis,10–20% of men with prostate cancer will develop CRPC.5

CRPC refers to the subset of men whose prostate cancer progresses despite castrate levels of testosterone (i.e., less than 50 ng/dL).6 Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases), and there is a rising PSA level.6 Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.7,8

About Enzalutamide
Enzalutamide is an oral, once-daily androgen receptor signaling inhibitor. Enzalutamide directly targets the androgen receptors (AR) and exerts its effects on three steps of the AR signaling pathway:3

Inhibits androgen binding: Androgen binding induces a conformational change that triggers activation of the receptor3
Prevents nuclear translocation: Translocation of the AR to the nucleus is an essential step in AR-mediated gene regulation3
Impairs DNA binding: Binding of the AR to the DNA is essential for modulation of gene expression3
Enzalutamide is currently approved in Japan for castration-resistant prostate cancer9 and in July 2018 the United States Food and Drug Administration (FDA) broadened the approved indication for enzalutamide to include men with nmCRPC.10

Important Safety Information for Enzalutamide in the EU
For important Safety Information for enzalutamide please see the full Summary of Product Characteristics at: View Source

About XTANDI (enzalutamide) capsules in the U.S.

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer.

Important Safety Information for XTANDI in the U.S.

Warnings and Precautions
Seizure occurred in 0.4% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. Patients in the study had one or more of the following pre-disposing factors: use of medications that may lower the seizure threshold; history of traumatic brain or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.7% vs 1.2%). Grade 3-4 ischemic events occurred in 1.2% of patients on XTANDI versus 0.5% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures In the placebo-controlled clinical studies, falls occurred in 10% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 8% of patients treated with XTANDI and in 3% of patients treated with placebo. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

Embryo-Fetal Toxicity Safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI. XTANDI should not be handled by females who are or may become pregnant.

Adverse Reactions
The most common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in the XTANDI patients from the randomized placebo-controlled trials were asthenia/fatigue, decreased appetite, hot flush, arthralgia, dizziness/vertigo, hypertension, headache and weight decreased. In the bicalutamide-controlled study, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In the placebo-controlled study of metastatic CRPC (mCRPC) patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve mCRPC patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher adverse reactions were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an adverse event as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients. In the bicalutamide-controlled study of chemotherapy-naïve mCRPC patients, Grade 3-4 adverse reactions were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials in patients with mCRPC, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). In the placebo-controlled trial in patients with nmCRPC, Grade 1-4 neutropenia occurred in 8% of patients receiving XTANDI (0.5% Grade 3-4) and in 5% of patients receiving placebo (0.2% Grade 3-4).

Hypertension: In the two placebo-controlled trials in patients with mCRPC, hypertension was reported in 11% of XTANDI patients and 4% of placebo patients. Hypertension led to study discontinuation in <1% of patients in each arm. In the placebo-controlled trial in patients with nmCRPC, hypertension was reported in 12% of patients receiving XTANDI and 5% of patients receiving placebo.

Drug Interactions
Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

On September 24, 2018 ArQule, Inc. (Nasdaq: ARQL) reported that Paolo Pucci, Chief Executive Officer, and Marc Schegerin, Senior Vice President, Strategy, Communication and Finance, will present at the Cantor Global Healthcare Conference on October 1, 2018, at 2:55pm ET at the InterContinental New York Barclay Hotel in New York City (Press release, ArQule, SEP 24, 2018, View Source [SID1234529533]).

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The live webcast of the presentation will be available via the "Investors & Media" section of ArQule’s website, www.arqule.com, under "Events & Presentations." A replay of the webcast will be available shortly after the conclusion of the presentation.