On December 03, 2018 Oncobiologics, Inc. (NASDAQ:ONS) (the "Company") reported several key corporate events that enhance the Company’s ability to advance the development of its lead product candidate, ONS-5010, a proprietary ophthalmic bevacizumab product candidate for the treatment of wet age related macular degeneration (wet AMD) (Press release, Oncobiologics, DEC 3, 2018, View Source [SID1234616259]). These events are in conjunction with the recent disclosure of new details of the ONS-5010 program and the initiation of the first human clinical study, which the Company announced in November 2018.

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The Company has changed its name from Oncobiologics, Inc. to Outlook Therapeutics, Inc., effective immediately. The Company will continue to be listed on the Nasdaq Capital Market and its common stock and Series A warrants will begin trading under the ticker symbols "OTLK" and "OTLKW," respectively, beginning on Tuesday, December 4, 2018.

No action is required by stockholders with respect to the name change. The Company’s common stock has been assigned a new CUSIP number of 69012T 107 and its Series A warrants have been assigned a new CUSIP number of 69012T 115 in connection with the name change. Outstanding securities are not affected by the name change and will not need to be exchanged.

"We believe the timing of this corporate rebranding effectively signals the significance of the recent strategic shift in the business and the high value opportunity we are pursuing in the anti-VEGF ophthalmic market," said Lawrence A. Kenyon, President, Chief Executive Officer and Chief Financial Officer. "The progress we have made throughout 2018 in advancing the ONS-5010 program has brought us to this exciting new stage in the Company’s history. The path ahead is clear and we look forward to providing further updates as we execute upon our strategy."

Two Additions to Executive Leadership Team

The Company announced two additions to its executive leadership team with the appointments of Jeff Evanson as Chief Commercial Officer and Terry Dagnon as Chief Operating Officer.

"Jeff and Terry are welcome additions to the team as they are both highly respected ophthalmic industry veterans and bring extensive drug development expertise to our leadership team," said Mr. Kenyon. "Jeff has an exceptional commercial track record in the ophthalmic space and brings valuable experience and deep know-how in product launches and marketing. Terry is a highly skilled expert in the regulatory field and his extensive experience in strategic drug development will be valuable for moving ONS-5010 through advanced clinical development and into commercialization. In addition, they have been key advisors on the ONS-5010 program to date and we expect them to be integral to the success of the asset as we move forward," stated Mr. Kenyon.

"Joining Outlook Therapeutics is a tremendous opportunity," said Jeff Evanson, newly appointed Chief Commercial Officer. "I am enthusiastic about the commercial prospects for ONS-5010 and its potential to address a need for all patients suffering from wet AMD and other retinal diseases requiring anti-VEGF treatments. I look forward to working with Larry and the team at Outlook Therapeutics in leading the efforts to bring ONS-5010 to market and contributing to the Company’s success."

Jeff Evanson joins the Company with more than 25 years of commercial expertise, most notably with Novartis (Alcon) where he was the Vice President and Global Commercial Head of the Pharmaceutical Franchise between 2010 and 2014 where he was responsible for all aspects of strategy, portfolio (both internal and external opportunities), global brands, launches and campaigns. Prior to Novartis, Mr. Evanson spent 10 years at Medtronic in a variety of pre-commercialization and post-commercialization roles. Most recently, Mr. Evanson led Scott Three Consulting, LLC as Founder and President since April of 2018 and previously was a Managing Director in the Life Science Practice of Navigant. He received his MBA from the University of Minnesota (2001) and a BA in Chemistry from the University of St. Thomas in St. Paul Minnesota (1991). He serves on the Board of Directors of Children’s HeartLink and was formerly a two-term Board Member of Gillette Children’s Hospital in St. Paul, Minnesota, from 2008 to 2014.

Terry Dagnon has more than 20 years of regulatory experience with domestic and global investigational and marketing approvals in the pharmaceutical and medical device industries. He is also experienced in quality and compliance and working with R&D, marketing, sales, legal, and manufacturing, quality and supply chain organizations. Most recently, Mr. Dagnon was Senior Vice President of Operations at Dohmen Life Science Services (DLSS), where he worked with companies to mitigate their compliance risk, ensure quality, and achieve FDA approval for pharmaceutical, biologics, and medical device products. Mr. Dagnon began his career in the pharmaceutical industry as the Regulatory Affairs Manager for Physician Reliance Network Inc. (now known as U.S. Oncology). He continued his regulatory affairs career at Johnson & Johnson Medical Inc. with global regulatory responsibility for the Wound Care, Skin Care and Tissue Engineering franchises. He then served as the North America Head of Regulatory Affairs at Alcon a Novartis company prior to joining DLSS in March 2014. Prior to a career in the medical industry, Mr. Dagnon served 11 years on active duty with the United States Army and was a SFC/E-7 Special Forces Green Beret 18D Senior Non-Commissioned Officer. Mr. Dagnon serves on the Board of Directors of the Colorado Bioscience Association.

Private Placement Proceeds

The Company announced today that it closed on the second tranche (of four) of its $20.0 million private placement of common stock to BioLexis Pte. Limited (BioLexis), the Company’s strategic business partner and largest investor, receiving $4.0 million of cash proceeds in exchange for the issuance of 4,288,624 shares of common stock at $0.9327 per share. The Company has received $12.0 million to date from the sale of its common stock to BioLexis under this private placement, which was previously announced on November 6, 2018. The remaining $8.0 million will be funded in two equal tranches on each of January 3, 2019 and February 1, 2019, subject to achieving certain funding milestones as set forth in the purchase agreement. The Company intends to use the net proceeds from the private placement primarily for clinical trials for its lead product candidate, ONS-5010, and for working capital and general corporate purposes, including agreed repayments on its senior secured notes.

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

On December 3, 2018 Significant developments in breast cancer research reported that it will be presented by NantHealth (NASDAQ: NH) at the San Antonio Breast Cancer Symposium this week (Press release, NantHealth, DEC 3, 2018, View Source;p=RssLanding&cat=news&id=2378988 [SID1234531804]). NantHealth, a leader in breakthrough cancer research and solutions to improve patient care and lower healthcare costs, will discuss the findings of three investigations, which examine the theme of providing oncologists with insights that enable cancer treatment tailored to the individual characteristics of each patient.

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The Symposium, which will be held at the Henry B. Gonzalez Convention Center in San Antonio from Dec. 4-8, is designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis and therapy of breast cancer and premalignant breast disease, to an international audience of academic and private physicians and researchers.

"About 1 in 8 U.S. women or about 12.4% will develop invasive breast cancer over the course of her lifetime. Such staggering statistics make breast cancer research and progress critical," said Sandeep "Bobby" Reddy MD, Chief Medical Officer, NantHealth. "We are honored to have an integral role at the San Antonio Breast Cancer Symposium, which provides a dynamic forum for interaction, communication, and education for a broad spectrum of researchers, health professionals, and those with a special interest in breast cancer."

Title: "Germline potentially pathogenic variants in breast cancer intrinsic molecular subtypes are not associated with somatic TMB"
Presenting Author: Elias Obeid, MD, MPH
Senior Author: Christopher Szeto, PhD
Contributors: Sandeep "Bobby" Reddy MD; Lori J. Goldstein, MD; Mary B. Daly, MD, PhD; Stephen C. Benz, PhD; and Michael J. Hall, MD, MS
Description: Comprehensive DNA and RNA profiling of 270 patients revealed intrinsic molecular subtypes of breast cancer have significantly distinct profiles of pathogenic germline variants. However, despite some breast cancer subtypes having higher frequency of germline pathogenic variants within DNA-damage repair genes, there is little evidence that these patients have subsequently higher mutational burden within their somatic genomes.
Key Takeaway: Pathogenic germline variants in key DNA damage repair genes such as BRCA1/2 are likely not adequate biomarkers for immune checkpoint therapy response, but are potentially biomarkers of differential tumorigenesis pathways.

Title: "Time-course DNA and RNA profiling of tumors from intra-patient cross-over trial of sequential use of aromatase inhibitors"
Presenting Author: Charles Vaske
Senior Authors: Vessela Kristensen and Jürgen Geisler
Contributors: Rahul Parulkar, Nazli Bahrami, Torill Sauer, Marie Loeng, Berit Gravdehaug, Belal Aljabri, Vahid Bemanian, Jonas Lindstrøm and Torben Lüders
Description: Early analysis from the ongoing NEOLETEXE trial examines a time-series of biopsies taken while transitioning patients from steroidal to non-steroidal aromatase inhibitors (AI) and vice versa. Acquired markers of AI-therapy resistance, and potential markers of sequential therapy sensitization, were explored. Two months after initial therapy, mutational burden decreased and clonality increased, yet by 4mo post-initialization mutations particularly in PIK3CA had repopulated.
Key Takeaway: Switching AI therapies sequentially in a clinical study is a model system to study differences in anti-tumor-effects of AIs. This ongoing trial may lead to a novel strategy to resensitize tumors to hormonal treatment and to elucidate the differences between steroidal and non-steroidal AIs.

Title: "Identification of a neoantigen targeted by tumor-infiltrating lymphocytes in a patient with Her2+ breast cancer"
Presenting Author: Hannah Kranich
Senior Authors: Peter A. Fasching and Anita N. Kremer
Contributors: Andrew Nguyen, Hanna Hübner, Erber Ramona, Judith Bausenwein, Edith D. van der Meijden, Michael P. Lux, Sebastian Jud, Claudia Rauh, John Zachary Sanborn, Stephen C. Benz, Shahrooz Rabizadeh, Matthias W. Beckmann, Andreas Mackensen and Matthias Rübner
Description: In our study, we identify tumor infiltrating T-cells (TILS) that recognize tumor specific mutations (Neoepitopes) found by next-generation sequencing of breast cancer tumors. These identified TILS are further immortalized and characterized to bind the patient’s specific HLA alleles.
Key Takeaway: Identification of TILS recognizing patient specific neoepitopes allow development of personalized medicine in a pre-clinical setting.

Since 1977, the San Antonio Breast Cancer Symposium mission has been to provide state-of-the-art information on breast cancer research. From a one-day regional conference, the Symposium has grown to a five-day program attended by a broad international audience of academic and private researchers and physicians from over 90 countries. For more information visit: View Source

On December 3, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") reported updated results from a Phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in patients newly diagnosed with FLT3 mutation-positive (FLT3mut+) Acute Myeloid Leukemia (AML) (Press release, Astellas, DEC 3, 2018, View Source [SID1234531821]). The data were presented today in an oral presentation (Abstract 564) at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"A diagnosis of AML can be devastating for patients. It is a life-threatening disease and treatment usually needs to start as quickly as possible," said Keith W. Pratz, M.D., of John Hopkins Sidney Kimmel Comprehensive Cancer Center, who presented the data at the ASH (Free ASH Whitepaper) Annual Meeting. "Typical treatment for AML consists of induction and consolidation therapy. However, treatment options targeted for specific mutations may be important tools in physicians’ armamentarium of therapies for patients with AML. These results help advance our scientific understanding of how to potentially address these mutations in first-line treatment of AML."

The purpose of this ongoing, open-label dose escalation/expansion Phase 1 clinical study (NCT02236013) is to assess the safety, tolerability and antitumor effects of gilteritinib when combined with induction and consolidation chemotherapy, and as single-agent maintenance therapy, in adult patients with newly diagnosed AML.1

The two-part trial first enrolled patients to successive cohorts to determine the Maximum Tolerated Dose. Patients in the dose expansion cohort received gilteritinib at the recommended expansion dose established during dose escalation.

As of October 11, 2018, 68 subjects had been enrolled in the study; 66 are included in the safety analysis set. Of these patients, 36 (54.5%) had FLT3 mutations (FLT3-ITD, n=26). During dose-escalation, two patients in the 40 mg/day cohort who had received gilteritinib on days 1-14 experienced dose-limiting toxicities (DLTs; neutropenia, thrombocytopenia, decreased ejection fraction). After the gilteritinib induction schedule change, no more DLTs occurred at this dose. Two patients in the 200 mg/day cohort experienced DLTs (neutropenia, neutropenic enterocolitis). The maximum tolerated dose and the recommended expansion dose were established at 120 mg/day.

Additional key findings include:

The end-of-treatment investigator-reported rate of composite complete remission (CRc) for response evaluable FLT3mut+ subjects receiving gilteritinib 120 mg on Schedule 1 (n=17) was 100%.
The CRc rate in FLT3mut+ subjects receiving Schedule 2 induction with daunorubicin was also 100%.
The CRc rate in FLT3mut+ subjects receiving Schedule 2 induction with idarubicin was 66.7%.
Among subjects who received ≥80 mg/day gilteritinib (n=52), the CRc rate for FLT3mut+ subjects was 90.3% (n=28/31).
Median overall survival has not been reached. Median disease-free survival was 430 days (95% CI: 155, 630).
Grade ≥3 adverse events (AEs) in ≥10% of subjects were febrile neutropenia (63.6%), thrombocytopenia (19.7%), decreased platelet count (19.7%), decreased white blood cell count (19.7%), neutropenia (19.7%), decreased neutrophil count (16.7%), anemia (13.6%), and sepsis (10.6%).
Serious drug-related AEs in >1 subject were febrile neutropenia (n=11), sepsis (n=4), small intestinal obstruction, and decreased ejection fraction (both n=2).
Gilteritinib, under the brand name XOSPATA, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation as detected by an FDA-approved test.2 Gilteritinib is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations.

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a cancer that impacts the blood and bone marrow, and its incidence increases with age. The American Cancer Society estimates that in 2018, approximately 19,000 new patients will be diagnosed with AML in the U.S.3

About XOSPATA
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.2 XOSPATA is also approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations.

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize XOSPATA.

Important Safety Information

Contraindications
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

Warnings and Precautions
Posterior Reversible Encephalopathy Syndrome (PRES) There have been rare reports of PRES with symptoms including seizure and altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XOSPATA in patients who develop PRES.

Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patients treated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

Adverse Reactions
The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%).

Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (7%), cardiac failure (grouped terms) (4%), pericardial effusion (3%), pericarditis (2%), differentiation syndrome (1%), anaphylactic reaction (1%) and posterior reversible encephalopathy syndrome (1%).

Lab Abnormalities: The most common lab abnormalities (>20%) that were Grade ≥3 that occurred ≥10% were: hypophosphatemia (12%), alanine aminotransferase increased (12%), hyponatremia (12%), aspartate aminotransferase increased (10%).

Drug Interactions

Combined P-gp and Strong CYP3A Inducers: Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure, which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.

Strong CYP3A inhibitors: Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.

Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor: Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.

Specific Populations
Lactation: Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

On December 3, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported results from a prospective Phase 2 single-arm, open-label, multicenter clinical trial studying the management of oral mucositis with the use of oral leucovorin (d,l-folinic acid) as adjunct to FOLOTYN (pralatrexate) in patients with hematological malignancies, including PTCL and CTCL (Press release, Spectrum Pharmaceuticals, DEC 3, 2018, View Source [SID1234531838]). These new data were highlighted in a poster presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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Study results with a total of 35 patients demonstrated that use of leucovorin 25 mg tablets by oral administration for two days (a total of six doses [150 mg cumulative weekly dose]), initiated 24 hours after each FOLOTYN dose (30 mg/m2 IV administration, once weekly for six weeks in each cycle) reduced the rate of Grade 2 or greater mucositis significantly, to 5.7 percent (95% CI = 1 – 19%) from historic rate (52%) associated with FOLOTYN use. There were no reports of ≥ Grade 3 oral mucositis. Grade 1 oral mucositis was reported only in 4 (11%) patients. No patient omitted, delayed or reduced FOLOTYN dose due to oral mucositis with adjunct leucovorin therapy. The occurrence of mucositis, an impediment of FOLOTYN, has previously been reported at a rate of 52 percent at Grade 2 or higher in patients undergoing treatment with FOLOTYN in a registration study (PROPEL).1

"Mucositis is a frequent complication of FOLOTYN therapy, which can cause painful inflammation of the digestive tract. It is often managed by omitting, delaying, or reducing the dose of this medication in some patients," said Andrei R Shustov, MD, lead investigator, professor of medicine, hematology, University of Washington School of Medicine, and hematologist, Seattle Cancer Care Alliance. "We are excited about how significantly leucovorin was able to reduce the rate of mucositis in patients and believe this study established the foundation for the potential use of leucovorin as a preventive regimen for FOLOTYN patients."

"While previous studies have established the use of FOLOTYN as an option in relapsed or refractory PTCL patients, mucositis has been an issue that could impact treatment and quality of life," said Francois Lebel, MD, Chief Medical Officer, Spectrum Pharmaceuticals. "This is the first prospective study to suggest that leucovorin may prevent or reduce oral mucositis. These are welcome findings that merit further studies of leucovorin as an adjunct to FOLOTYN so we can one day provide definitive guidance to physicians to help reduce concerns of FOLOTYN treatment delay or discomfort due to oral mucositis."

About FOLOTYN

FOLOTYN, (pralatrexate injection), a folate analogue metabolic inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI International and Southern Research Institute and developed by Allos Therapeutics. In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from PROPEL, the pivotal study of FOLOTYN in patients with relapsed or refractory PTCL, was published in the March 20, 2011 issue of the Journal of Clinical Oncology.

Important FOLOTYN Safety Information

Warnings and Precautions

FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.

Mucositis may occur. If greater-than or equal to Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.

Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may occur. Monitor patients and treat if needed.

FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.

Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.

Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are greater-than or equal to Grade 3, omit or modify dose.

Adverse Reactions

The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.

Use in Specific Patient Population

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

Drug Interactions

Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.

On December 3, 2018 AstraZeneca and Acerta Pharma, its haematology research and development centre of excellence, have presented new, long-term follow-up results for Calquence (acalabrutinib) in patients with relapsed or refractory mantle cell lymphoma (MCL), and updated results of an ongoing clinical trial assessing Calquence monotherapy in treatment-naïve patients with chronic lymphocytic leukaemia (CLL), at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego, CA, USA (Press release, AstraZeneca, DEC 3, 2018, View Source [SID1234531822]).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "The data from these two clinical trials validate previous findings and add to the growing body of evidence that support the promise of Calquence in multiple blood cancers. We are very encouraged by these results, which reinforce our commitment to advancing innovative treatments for blood cancer patients."

Calquence follow-up data in MCL confirms efficacy and tolerability

Long-term follow-up data presented from the Phase II ACE-LY-004 trial in relapsed or refractory MCL showed sustained and clinically meaningful responses to Calquence with a median follow-up of more than two years (26 months), confirming its efficacy and safety profile in this patient population.1 Initial data from this trial served as the basis for the accelerated approval of Calquence by the US Food and Drug Administration in October 2017 and the first approval outside the US in November 2018 in the United Arab Emirates.3,4

Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL trial, said: "It’s encouraging to see the sustained duration of response in the updated analysis and the safety profile of acalabrutinib maintained consistently over time in MCL patients. As we gain more and more experience with this therapy, its importance as a treatment option for relapsed or refractory MCL is being more fully realised across the clinical and patient community."

Summary of key investigator-assesseda efficacy results from the open-label, single-arm clinical trial of Calquence in 124 adult patients with relapsed or refractory MCL1:

Efficacy measure Result (N=124; 95% CIb)
Overall response rate

(Complete response + partial response)

81% (73, 87)

Best response

Complete response

43% (34, 52)

Partial response

38% (29, 47)

Stable disease

9% (5, 15)

Progressive disease

8% (4, 14)

Not evaluablec

2% (1, 7)

Median duration of response

26 months (17.5, not reached)

Median progression-free survival

20 months (16.5, 27.7)

a Response was assessed based on the Lugano classification.

b Confidence interval (CI).

c Includes patients without any adequate post-baseline disease assessment.

The median follow-up was 26 months, with 40% of patients remaining on treatment with Calquence at the time of analysis. An exploratory analysis of the trial found that an undetectable minimal residual disease status was achieved in a sub-set of patients.

In this trial, the most frequent adverse events (AEs; ≥ 20%, all grades) were headache (38%), diarrhoea (36%), fatigue (28%), cough (22%) and myalgia (21%). These events were primarily Grade 1/2. Grade 3/4 AEs (≥ 5%) were anaemia (11%), neutropoenia (11%) and pneumonia (6%). There were 13 patients (10%) with 16 cardiac events including four Grade 3/4 events, each in one patient (acute coronary syndrome, acute myocardial infarction, cardiorespiratory arrest, coronary artery disease). There was no new onset of atrial fibrillation. Bleeding events occurred in 33% of patients, most frequently contusion (13%) and all bleeding events but three (2%, Grade 3) were Grade 1/2 events. Ten patients discontinued treatment due to AEs. In total there were six deaths due to AEs (none of which were considered to be related to Calquence).1

New data from ongoing CLL clinical trial demonstrate strong efficacy

Updated results of the Phase I/II ACE-CL-001 trial were presented today in an oral session. In a cohort of treatment-naïve patients with CLL, long-term safety and efficacy of assessment showed high response rates with no new safety signals identified. The median time on trial was 42 months, with 89% of patients remaining on treatment with Calquence at the time of analysis.2

John C. Byrd, MD, Distinguished University Professor, The Ohio State University, and Principal Investigator for the ACE-CL-001 CLL clinical trial, said: "A key challenge in the treatment of CLL is ensuring patients have therapies that they can tolerate and benefit from over the long term. The results seen in this patient cohort at 3.5 years of follow-up are encouraging for both durability of response and tolerability of therapy. We look forward to continued data from ongoing studies evaluating acalabrutinib in CLL."

Summary of key investigator-assesseda efficacy results from the Phase I/II open-label, single-arm ACE-CL-001 Calquence trial in 99 patients with CLL, evaluating the treatment-naïve cohort2:

Efficacy measure Result (N=99)
Overall response rate

(Complete response + partial response)

97%

Complete response

5%

Partial response

92%

Median duration of responseb

NR (range, 42.4 to NR)c

36 month duration of response rate (95% CI)b,d,e

98% (90, 99)

Median progression-free survival

NR (range, 44.2 to NR)c

36 month progression-free survival rate (95% CI)d,e

97% (91, 99)

a Response was assessed using International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria with modification for lymphocytosis.

b Only responders with ≥ partial response were included in this analysis.

c Not reached (NR).

d Confidence interval (CI).

e Based on the Kaplan-Meier estimates.

In this trial, the most common AEs (≥ 20%, all grades) were diarrhoea (49%), headache (44%), upper respiratory tract infection (40%), contusion (39%), arthralgia (33%), weight increased (31%), nausea (30%) and cough (23%). Grade 3/4 AEs (≥ 5%) were neutropenia (8%), hypertension (7%), diarrhoea (5%) and headache (5%). Atrial fibrillation and hypertension (all grades) occurred in 6% and 17% of patients, respectively, with Grade 3 events occurring in 2% and 7% of patients. Bleeding events (all grades) occurred in 64% of patients with contusion being most common (39%). All but three (3% Grade 3) bleeding events were Grade 1/2 events and no patients discontinued due to bleeding. Overall, 11% of patients discontinued treatment, 5% of which were due to AEs, including secondary malignancies (angiosarcoma, glioblastoma multiforme, small cell lung cancer), sepsis (Grade 4) and urinary tract infection (Grade 3). One Grade 5 event (multiorgan failure) in the setting of pneumonia was reported, which was considered unrelated to Calquence.2

NOTES TO EDITORS
About Calquence

Calquence (acalabrutinib) is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3 In B cells, BTK signalling results in activation of pathways necessary for B cell proliferation, trafficking, chemotaxis, and adhesion.3

Calquence was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Calquence is not currently licensed for the treatment of chronic lymphocytic leukaemia (CLL).

Calquence was granted Orphan Drug designation by the European Commission in 2016 and the US FDA in 2015 for the treatment of patients with CLL, MCL and Waldenstrom’s macroglobulinemia; and Breakthrough Therapy Designation in August 2017 by the US FDA for the treatment of patients with MCL who have received at least one prior therapy.

About mantle cell lymphoma (MCL)

MCL is an uncommon type of B-cell non-Hodgkin lymphoma.5,6,7 MCL comprises 3% to 6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it was estimated that approximately 3,300 new cases of MCL were diagnosed in 2016.5,8 The median age at diagnosis is 68 years,5 with MCL occurring more than twice as often in men than women.7 While MCL patients initially respond to treatment, there is a high relapse rate.5

About chronic lymphocytic leukaemia (CLL)

CLL is the most common type of leukaemia in adults and accounts for approximately one in four cases of leukaemia.9,10 The average age at the time of diagnosis is approximately 70 years of age.10 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.9 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.9 This could result in anaemia, infection and bleeding.9 B cell receptor signalling through BTK is one of the essential growth pathways for CLL