1stOncology™: Cancer Intelligence Service – Page 12081 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

CStone announces first patient dosed in the Phase I bridging registrational study of ivosidenib

On November 19, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that the first patient has been dosed in the Phase I bridging registrational study of ivosidenib (TIBSOVO) in China (Press release, CStone Pharmaceauticals, NOV 19, 2019, View Source [SID1234551490]). This stand-alone trial is designed to validate the efficacy, safety, and pharmacokinetics of ivosidenib in patients with IDH1 mutant relapsed or refractory acute myeloid leukemia (R/R AML).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Developed by CStone’s partner, Agios Pharmaceuticals (NASDAQ: AGIO), ivosidenib was approved by the U.S. FDA in July 2018 for the treatment of adult patients with R/R AML with a susceptible IDH1 mutation as detected by an FDA-approved test. In May 2019, CStone submitted a new drug application (NDA) for ivosidenib in Taiwan for the treatment of adult patients with IDH1 mutant R/R AML.

Current standard of care treatment for newly diagnosed AML patients mainly includes intensive induction chemotherapy (IC), followed by consolidation therapy such as allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in order to attain durable remission. Approximately 35% to 40% of those treated patients achieve complete remission, while only about 25% achieve 3 years or longer survival. The majority of AML patients develop acquired resistance to treatment or eventually relapse, leading to R/R AML, which has a very poor prognosis in the absence of standard of care treatment options globally. With the emergence of DNA sequencing technology, the detection of genetic mutations has presented new opportunities and challenges in AML treatment. IDH1 mutations are associated with around 6% to 10% of all AML cases.

Dr. Frank Jiang, Chairman and CEO of CStone, commented: "AML is the most common acute leukemia affecting adults with over 30,000 new cases estimated in China every year. AML is characterized by its rapid progression with a five-year survival rate below 20%. We are faced with the urgent need for clinical development, particularly for IDH1 mutant R/R AML patients, due to the lack of any effective treatment in China. We will rigorously press ahead with the clinical development of ivosidenib to achieve its regulatory approval in China which will allow more AML patients in Greater China to benefit from this precision therapy."

CStone’s Chief Medical Officer, Dr. Jason Yang, noted: "Ivosidenib is a potent and highly selective IDH1 inhibitor, and the only targeted therapy currently approved by the U.S. FDA for IDH1 mutant AML. It is very encouraging that we have already initiated two registrational studies of ivosidenib in China, including the global Phase III AGILE study of ivosidenib in combination with azacitidine in adult patients with newly diagnosed IDH1 mutant AML who are not eligible for intensive chemotherapy."

About TIBSOVO (ivosidenib)

TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Adult patients with relapsed or refractory AML.
IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions including laboratory abnormalities (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

Lucence Raises USD $20M Series A Led by IHH Healthcare to Advance Liquid Biopsy for Early Detection of Multiple Cancers

On November 19, 2019 Lucence, a genomic medicine company that invents blood-based tests for cancer screening and treatment selection, reported the close of USD $20 million in Series A funding (Press release, Lucence, NOV 19, 2019, View Source [SID1234551489]). The round was led by IHH Healthcare, one of the world’s largest integrated private healthcare groups. SGInnovate, together with existing investors Temasek Holdings subsidiary Heliconia Capital, Lim Kaling, Koh Boon Hwee and others, also participated in the round. This funding will enable the company to provide its liquid biopsy technology to more patients across Asia and North America for personalized treatment selection. Lucence will also embark on new prospective clinical studies to evaluate its technology for the early detection of multiple cancers.

Lucence spun out of Singapore’s Agency for Science, Technology and Research (A*STAR) in 2016. In 2018, the company introduced its flagship next-generation sequencing test, LiquidHALLMARK, the first and only clinical sequencing blood test that detects both cancer-related gene mutations and cancer-causing viruses within a single assay. The test has been used by oncologists in cancer diagnosis, monitoring and treatment selection for over 1,000 patients in Asia to date. LiquidHALLMARK detects clinically relevant mutations across 14 cancer types, including lung, breast, colorectal, pancreatic, nasopharyngeal and liver cancers. The test is based on Lucence’s core molecular watermarking technology, AmpliMARK, for improved accuracy and depth in sequencing results. In 2019, Lucence’s Singapore central laboratory became the first laboratory in Southeast Asia to be CLIA-certified and CAP-accredited in order to bring LiquidHALLMARK to physicians and patients in the United States.

"Our mission is to reduce worldwide suffering through early cancer detection. As a medical oncologist, I have worked in the clinic and the laboratory for over a decade, striving towards a world where cancer can be overcome with early screening. Our research discoveries, such as the identification of the circulating tumor-endothelial cluster, can transform the liquid biopsy field, allowing better non-invasive cancer screening and profiling for patients. This partnership with IHH Healthcare will accelerate our work to achieve early cancer detection and effective cures, and expand access to this much-needed liquid biopsy technology to patients across Asia and the United States," said Dr. Min-Han Tan, MBBS, PhD, founder and CEO of Lucence.

Dr. Kelvin Loh, Chief Executive Officer (Designate) of IHH Healthcare, said, "Liquid biopsy is a game-changer in our endeavor to provide cancer patients with better, value-driven outcomes through precise treatment selections and more affordable care. Our investment in Lucence will provide IHH patients with better access to this advanced technology. IHH looks to drive greater synergies with Lucence and co-develop solutions for patients, as well as explore opportunities to sharpen our precision medicine capabilities with other like-minded partners across our 10-country network."

Lucence will be in attendance at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress this week and will be exhibiting at booth B09.

Personalis to Present at Upcoming Investor Conferences

On November 19, 2019 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported that Aaron Tachibana, Chief Financial Officer and Clinton Musil, Chief Business Officer, are scheduled to present at the following upcoming investor conferences (Press release, Personalis, NOV 19, 2019, View Source [SID1234551488]).

Piper Jaffray 31st Annual Healthcare Conference on Wednesday, December 4, 2019 at 11:30 a.m. Eastern Time at the Lotte New York Palace Hotel in New York.
Evercore ISI 2nd Annual HealthCONx Conference on Thursday, December 5, 2019 at 11:00 a.m. Eastern Time at the Four Seasons Hotel in Boston.

Janssen Receives EU Marketing Authorisation for Darzalex®▼(daratumumab) in Combination with Lenalidomide and Dexamethasone for Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Ineligible

On November 19, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the European Commission (EC) has granted marketing authorisation for Darzalex(daratumumab) in combination with lenalidomide and dexamethasone (DRd) for the treatment of newly diagnosed multiple myeloma patients who are ineligible for autologous stem cell transplant (ASCT) (Press release, Janssen Pharmaceuticals, NOV 19, 2019, View Source [SID1234551487]). The approval was based on results from the Phase 3 MAIA (MMY3008) study, published in The New England Journal of Medicine3 earlier this year and presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in 2018.

"Despite recent therapeutic advances, relapse of multiple myeloma is considered to be almost inevitable, becoming more challenging to treat following each relapse. This makes it even more important that we maximise our best response upfront to extend the first remission," said Professor Thierry Facon, M.D., Service des Maladies du Sang, Hôspital Claude Huriez, Lille, France, and principal investigator of the MAIA study. "This marks an important approval, especially for transplant ineligible patients, a more vulnerable population, for whom outcomes are generally poorer when compared to those who are transplant eligible."

The study included 737 newly diagnosed patients with multiple myeloma ineligible for high-dose chemotherapy and ASCT aged 45-90 years old (median age of 73 years).1 Daratumumab in combination with Rd significantly reduced the risk of disease progression or death by 44 percent in patients with newly diagnosed multiple myeloma who are transplant ineligible, compared to treatment with Rd alone (Hazard Ratio [HR] = 0.56; 95 percent confidence interval [CI]: 0.43-0.73; p<0.0001).1 At median follow-up of 28.0 months the median progression-free survival (PFS) for daratumumab-Rd had not yet been reached, compared to 31.9 months for patients who received Rd alone.1 The addition of daratumumab resulted in deeper responses compared to Rd alone, including increased rates of complete response (CR) or better (48 percent vs. 25 percent) and improved rates of very good partial response (VGPR) or better (79 percent vs. 53 percent).1 Daratumumab-Rd induced a >3-fold higher rate of minimal residual disease (MRD) negativity compared to those who received Rd alone (24 percent vs. 7 percent).1

"Every year over 48,000 people in Europe are diagnosed with multiple myeloma, which is considered to be incurable. Older patients who are ineligible for transplant have a limited range of frontline therapeutic options available, so we are pleased that with today’s approval of daratumumab-Rd, these patients now have a new frontline option available to them," said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag.

Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC., commented: "It’s gratifying to see that through our research and development efforts, daratumumab has helped over 100,000 patients globally. With today’s approval and the continued development of daratumumab, we hope to bring this innovative therapy to many more patients in the future."

The most common Grade 3/4 treatment-emergent adverse events (TEAEs) for daratumumab-Rd (≥10 percent) included neutropenia (50 percent), lymphopenia (15 percent), pneumonia (14 percent) and anaemia (12 percent).1 Infusion-related reactions (IRRs) occurred in 41 percent of patients, only 3 percent of which were Grade 3/4.1 Incidence of invasive second primary malignancy was 3 percent in the daratumumab-Rd arm compared to 4 percent with Rd alone.1 TEAEs with an outcome of death were 7 percent in the daratumumab-Rd arm compared to 6 percent in the Rd arm.1 The safety profile of daratumumab was consistent with that of previous studies.1

In Europe, daratumumab is indicated:4

in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant,
in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy,
as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent, and who have demonstrated disease progression on the last therapy.
#ENDS#

About the MAIA (NCT02252172) Trial5

In this open-label and multicentre Phase 3 study patients were randomised to receive either daratumumab-Rd or Rd alone in 28-day Cycles. In the daratumumab-Rd treatment arm, patients received daratumumab 16 (mg/kg) IV weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every 4 weeks for Cycle 7 and thereafter. The primary endpoint was Progression-Free Survival, defined as the time from date of randomisation to either progressive disease, or death, whichever occurred first. Patients in the daratumumab-Rd and Rd treatment arm received 25 mg of lenalidomide on Days 1 – 21 of each 28-day Cycle, and dexamethasone at 40 mg once a week for each Cycle. Patients in both treatment arms continued until disease progression or unacceptable toxicity.

About daratumumab

Daratumumab is a first-in-class6 biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.7 Daratumumab is believed to induce tumour cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.4 A subset of myeloid derived suppressor cells (CD38+ MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by daratumumab.4 Since launch, it is estimated that 100,000 patients have been treated with daratumumab worldwide.2 Daratumumab is being evaluated in a comprehensive clinical development programme across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.5,8,9,10,11,12,13,14 Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant haematologic diseases in which CD38 is expressed, such as smouldering myeloma.15,16 For more information, please see View Source

For further information on daratumumab, please see the Summary of Product Characteristics at View Source

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive licence to develop, manufacture and commercialise daratumumab.17

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.18 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.19 Almost 60 percent of patients with MM do not survive more than five years after diagnosis.20

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.21 Refractory MM is when a patient’s disease progresses within 60 days of their last therapy.22,23 Relapsed cancer is when the disease has returned after a period of initial, partial or complete remission.24 While some patients with MM have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.25 Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.26

Positive Pivotal Data for Daiichi Sankyo’s DS-8201 ([Fam]-Trastuzumab Deruxtecan) in Patients with HER2 Positive Metastatic Breast Cancer to be Presented at SABCS

On November 19, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it will present new data across its investigational ADC portfolio at the 2019 San Antonio Breast Cancer Symposium (#SABCS19), December 10-14, 2019 in San Antonio, Texas (Press release, Daiichi Sankyo, NOV 19, 2019, https://www.businesswire.com/news/home/20191119005106/en/Positive-Pivotal-Data-Daiichi-Sankyo%E2%80%99s-DS-8201-Fam [SID1234551486]).

Positive data from the pivotal phase 2 DESTINY-Breast01 trial of DS-8201 ([fam-] trastuzumab deruxtecan), an investigational HER2 targeting antibody drug conjugate (ADC), will be unveiled, highlighting objective response rate, progression-free survival, duration of response and safety seen in patients with HER2 positive metastatic breast cancer previously treated with ado-trastuzumab emtansine.

Trial-in-progress updates from the pivotal phase 3 development program of DS-8201 in patients with HER2 positive metastatic breast cancer, including a head-to-head study with ado-trastuzumab emtansine, and in patients with HER2 low metastatic breast cancer, also will be presented. An overview of the phase 1/2 trial for U3-1402, an investigational HER3 targeting ADC, in HER3 expressing advanced/unresectable or metastatic breast cancer also will be featured at SABCS.

"Following the recent Priority Review acceptance of our BLA by the FDA and our regulatory submission in Japan, we look forward to presenting the pivotal results of DS-8201 monotherapy in patients with HER2 positive metastatic breast cancer at SABCS," said Antoine Yver, MD, MSc, EVP and Global Head, Oncology Research and Development, Daiichi Sankyo. "These data, coupled with other important scientific discussions surrounding our other pivotal studies in HER2 positive and HER2 low metastatic breast cancer, underscore the commitment we have in bringing DS-8201 to as many patients as possible."

The ADC portfolio of Daiichi Sankyo currently consists of seven novel ADCs, with four in clinical development across multiple types of cancer, including DS-8201, which is being co-developed and co-commercialized globally with AstraZeneca; U3-1402 (targeting HER3); DS-1062 (targeting TROP2) and DS-7300 (targeting B7-H3). Each ADC is engineered and designed using Daiichi Sankyo’s proprietary DXd ADC technology, which consists of a monoclonal antibody attached by a tetrapeptide-based linker to a novel topoisomerase I inhibitor payload. Each ADC is constructed to target and deliver chemotherapy inside cancer cells that express a specific cell surface antigen, and each has a customized drug to antibody ratio (DAR) designed to optimize the risk-benefit ratio for the intended patient population.

Following SABCS, Daiichi Sankyo will hold its first-ever U.S.-based R&D Day for investors and analysts on Thursday, December 19, 2019 at 10:30 AM ET at the New York Hilton Midtown in New York, NY. Company executives will provide an overview of the DS-8201 data presented at SABCS, unveil a new R&D strategy, including updated clinical development plans across the investigational ADC portfolio, and address questions from investors and analysts. Investors are invited to register for R&D Day by emailing [email protected] prior to the event.

Following is an overview of data from Daiichi Sankyo to be presented at SABCS:

SABCS Abstract

Presentation Details

[Fam-] trastuzumab deruxtecan (T-DXd; DS-8201 in subjects with HER2-positive metastatic breast cancer (MBC) previously treated with T-DM1: A phase 2, multicenter, open-label study (DESTINY-Breast01)

Session Title: General Session 1
Date/Time: Wednesday, December 11, 2019; 9:15-9:30 AM CT
Location: Hall 3

A phase 1, multicenter, open-label study to assess the effect of [fam-] trastuzumab deruxtecan (T-DXd; DS-8201) on QTc and pharmacokinetics in subjects with HER2-expressing metastatic and/or unresectable breast cancer

Program Number: P1-18-12
Session Title: Poster Session 1
Date/Time: Wednesday, December 11, 2019; 5:00-7:00 PM CT
Location: Hall 1

A phase 3, multicenter, randomized, open-label trial of [fam-] trastuzumab deruxtecan (T-DXd; DS-8201) vs. investigator’s choice in HER2-low breast cancer (DESTINY-Breast04)

Program Number: OT1-07-02
Session Title: Antibody-Drug Conjugates
Date/Time: Wednesday, December 11, 2019; 5:00-7:00 PM CT
Location: Hall 1

[Fam-] trastuzumab deruxtecan (T-DXd; DS-8201) vs. ado-trastuzumab emtansine (T-DM1) in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received trastuzumab and a taxane: a phase 3, randomized trial (DESTINY-Breast03)

Program Number: OT1-07-01
Session Title: Antibody-Drug Conjugates
Date/Time: Wednesday, December 11, 2019; 5:00-7:00 PM CT
Location: Hall 1

[Fam-] trastuzumab deruxtecan (T-DXd; DS-8201) vs. investigator’s choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received TDM-1: a randomized, phase 3 trial (DESTINY-Breast02)

Program Number: OT1-07-04

Session Title: Antibody-Drug Conjugates

Date/Time: Wednesday, December 11, 2019; 5:00-7:00 PM CT

Location: Hall 1

Phase 1/2 first-in-human study of U3-1402, an anti-human epidermal growth factor receptor 3 (HER3) antibody-drug conjugate, in HER3-expressing advanced/unresectable or metastatic breast cancer, including those with triple negative breast cancer (TNBC) or HER3-low disease

Program Number: OT1-07-06
Session Title: Antibody-Drug Conjugates
Date/Time: Wednesday, December 11, 2019; 5:00-7:00 PM CT
Location: Hall 1

Evaluation of patritumab/paclitaxel/trastuzumab over standard paclitaxel/trastuzumab in early stage, high-risk HER2 positive breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL

Program Number: P3-11-02
Session Title: Poster Session 3
Date/Time: Thursday, December 12, 2019; 5:00-7:00 PM CT
Location: Hall 1

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal phase 2, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of DS-8201 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with ado-trastuzumab emtansine. The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival. Enrollment into DESTINY-Breast01 was completed in September 2018 with 253 patients at more than 100 sites across North America, Europe, Japan and other countries in Asia.

The safety and tolerability profile of DS-8201 in DESTINY-Breast01 was consistent with the phase 1 trial data published in The Lancet Oncology,1 in which the most common adverse events (≥30 percent, any grade) included nausea, decreased appetite, vomiting, alopecia, fatigue, anemia, diarrhea and constipation. Cases of drug-related interstitial lung disease (ILD) and pneumonitis, including grade 5 events, have also been reported in the clinical development program.

About DS-8201

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 and the most advanced program in AstraZeneca’s ADC scientific platform.

In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize DS-8201 as a potential new medicine worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for the manufacturing and supply.

A comprehensive development program for DS-8201 is underway globally with five pivotal trials in HER2 expressing metastatic breast and gastric cancer, including a trial in patients with metastatic breast cancer and low levels of HER2 expression (HER2 low). Phase 2 trials are underway for HER2 expressing advanced colorectal cancer as well as metastatic non-squamous HER2 overexpressing or HER2 mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

The U.S. Food and Drug Administration (FDA) recently granted Priority Review for the Biologics License Application (BLA) for DS-8201 for the treatment of HER2 positive metastatic breast cancer, which previously received Breakthrough Therapy and Fast Track Designations. A regulatory submission for DS-8201 also has been made to Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of HER2 positive metastatic breast cancer, and it has previously received SAKIGAKE designation for the treatment of advanced HER2 positive gastric or gastroesophageal junction cancer by Japan’s MHLW.

About U3-1402

U3-1402 is an investigational and potential first-in-class HER3 targeting ADC currently in phase 1/2 development for HER3 expressing metastatic or unresectable breast cancer in the U.S. and Japan and phase 1 development for metastatic or unresectable non-small cell lung cancer in the U.S.

DS-8201, U3-1402, DS-1062 and DS-7300 are investigational agents that have 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 pipeline, 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. For more information, please visit: www.DSCancerEnterprise.com.