1stOncology™: Cancer Intelligence Service – Page 12609 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

RAPT Therapeutics Reports Third Quarter 2019 Financial Results and Recent Highlights

On December 11, 2019 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported financial results for the third quarter ended September 30, 2019 and provided an update on recent operational and business progress (Press release, RAPT Therapeutics, DEC 11, 2019, View Source [SID1234552256]).

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!

"We are pleased to report significant progress as a public company following our initial public offering," said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. "This includes clinical and operational advancement of our two lead compounds, FLX475 for oncology and RPT193 for allergic inflammatory disease. We recently announced a collaboration with Hanmi for FLX475 in Asia, a region with a high prevalence of ‘charged’ tumors. As we look toward 2020, we expect to report clinical proof of concept data for each program as we reach milestone events in our ongoing clinical trials."

Recent Highlights

Signed a license and collaboration agreement with Hanmi Pharmaceutical Co., LTD for the development and commercialization of FLX475 in Korea and China, including Taiwan and Hong Kong. RAPT will receive $10 million in an upfront payment and near-term milestone payment, and will receive up to $48 million in success-based development milestones and up to $60 million in potential sales milestones, as well as double-digit royalties on any future sales of FLX475 in the specified territories. In addition to leveraging its clinical trial infrastructure in Korea and China to augment RAPT’s ongoing Phase 1/2 clinical study of FLX475, Hanmi will conduct a Phase 2 clinical trial in Korea and China to evaluate FLX475 in patients with gastric cancer.

Continued enrolling patients with "charged" tumors in a Phase 1/2 study of FLX475 as a monotherapy and in combination with pembrolizumab.

Initiated a first-in-human Phase 1 study of RPT193, a CCR4 antagonist to treat allergic inflammatory diseases, including atopic dermatitis.

Completed its initial public offering (IPO), raising $33.8 million in net proceeds, which includes the underwriters’ exercise of their overallotment option to purchase additional shares at the IPO price. The Company’s stock commenced trading on the Nasdaq Global Select Market under the ticker symbol "RAPT."

Appointed Rodney Young as Chief Financial Officer.

Appointed Wendye Robbins, M.D., President and CEO of Blade Therapeutics, and Mary Ann Gray, Ph.D., President of Gray Strategic Advisors, LLC, to the Board of Directors.

Financial Results for the Third Quarter and Nine Months Ended September 30, 2019

Third Quarter ended September 30, 2019

Net loss for the third quarter of 2019 was $10.0 million, compared to $10.3 million for the third quarter of 2018.

Research and development expenses for the third quarter of 2019 were $8.6 million, compared to $9.2 million for the same period in 2018. The decrease was primarily due to decreases in costs relating to the clinical development of FLX475, outsourced research and development, and lab supplies, offset by increases in costs relating to the clinical development of RPT193 and personnel.

General and administrative expenses for the third quarter of 2019 were $1.7 million, compared to $1.4 million for the same period in 2018.

Nine Months Ended September 30, 2019

Net loss for the nine months ended September 30, 2019 was $29.8 million, compared to $26.7 million for the same period in 2018.

Research and development expenses for the nine months ended September 30, 2019 were $24.7 million, compared to $23.4 million for the same period in 2018. The increase was primarily due to increases in costs relating to the clinical development of RPT193, facilities and personnel, offset by decreases in costs relating to the clinical development of FLX475, lab supplies and outsourced research and development.

General and administrative expenses for the nine months ended September 30, 2019 were $6.1 million, compared to $3.9 million for the same period in 2018. The increase was primarily due to increases in professional service fees related to the Company’s preparation of its initial public offering.

As of September 30, 2019, the Company had cash and cash equivalents of $48.3 million. The Company completed its initial public offering on November 4, 2019 and received net proceeds of approximately $33.8 million, which includes the underwriters’ exercise of the overallotment option.

Puma Biotechnology Presents Results from the Phase II SUMMIT Trial of Neratinib for ERBB2 (HER2) Mutant, HER2 Non-Amplified, Metastatic Breast Cancer at the 2019 San Antonio Breast Cancer Symposium

On December 11, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that results from an ongoing Phase II clinical trial of Puma’s drug neratinib are being presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 11, 2019, View Source [SID1234552255]). The presentation entitled, "Neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer: updated results from the phase 2 SUMMIT ‘basket’ trial," are being presented at a poster Session by Hans Wildiers, M.D., Ph.D., University Hospitals Leuven, Belgium, an investigator of the trial. A copy of this poster presentation is available on the Puma website

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed in the United States as NERLYNX (neratinib) tablets. NERLYNX was granted marketing authorization by the European Commission for the extended adjuvant treatment of hormone receptor-positive HER2-positive early stage breast cancer in August 2018.

The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating HER2 or HER3 mutations. In the HER2-mutant, HR-positive breast cancer cohort, 28 patients received 240 mg of neratinib daily in combination with trastuzumab and fulvestrant. In this cohort, patients had received a median of 4 prior lines of therapy in the metastatic setting (range 0-10 prior regimens) before entering the trial. All patients had been previously treated with an endocrine agent prior to entering the study, including 17 patients (61%) who had received prior fulvestrant. Further, 15 patients (54%) received prior cyclin-dependent kinase 4/6 (CDK4/6) -inhibitor therapy. Twenty-one patients (75%) had received prior chemotherapy.

The interim efficacy summary of the breast cohort that received neratinib in combination with trastuzumab and fulvestrant showed that for the 17 efficacy evaluable patients, 9 patients (53%) experienced a confirmed objective response, all of which were classified as partial responses, and 10 patients (59%) experienced clinical benefit (clinical benefit is defined as confirmed complete response or partial response or stable disease for at least 24 weeks). The median duration of response has not been reached and the median progression-free survival was 9.8 months. At the time of data cut-off, five patients continued to receive treatment.

The safety profile observed in patients treated with the combination of neratinib plus trastuzumab plus fulvestrant in the SUMMIT study was consistent with that observed previously in metastatic patients with HER2 amplified tumors. All patients received anti-diarrheal prophylaxis with loperamide alone. The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 28 safety evaluable patients enrolled in this cohort, 10 patients (36%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for those patients was 5.5 days. No patient permanently discontinued neratinib due to diarrhea.

Prof. Dr. Hans Wildiers said, "The combination of neratinib plus trastuzumab plus fulvestrant therapy demonstrates encouraging clinical activity with durable responses in this heavily pretreated metastatic breast cancer patient population with activating HER2 mutations and hormone receptor-positive disease. We look forward to continuing to enroll this cohort of SUMMIT."

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the activity seen with neratinib in combination with trastuzumab and fulvestrant in this cohort of patients with HER2-mutated breast cancer. We are in the process of expanding this HR-positive breast cancer cohort in SUMMIT with the intent of using this data to support future registration. We look forward to enrolling additional patients into this HR-positive breast cancer cohort in order to generate the additional data required to support approval of this combination therapy."

Novartis Kisqali® data show superior overall survival compared to fulvestrant and consistent efficacy across advanced breast cancer patient subgroups in MONALEESA-3

On December 11, 2019 MONALEESA-3 data reported that published in The New England Journal of Medicine (NEJM) shows Kisqali (ribociclib) plus fulvestrant demonstrated a statistically significant improvement in overall survival, with an almost 30% reduction in risk of death compared to fulvestrant alone, in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer1 (Press release, Novartis, DEC 11, 2019, View Source [SID1234552254]). MONALEESA-3 overall survival data were first presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2019 (see media release). The NEJM publication includes new analyses confirming overall survival benefit across all patient sub-groups treated with Kisqali plus fulvestrant.

"These data show that treatment with Kisqali gives women with HR+/HER2- advanced breast cancer a chance for more life – whether they are treatment naïve or have had prior therapy," said Jeff Engelman, MD, PhD, Global Head of Oncology Research, Novartis Institutes for BioMedical Research. "Pre-clinical data show that Kisqali is distinct from other CDK4/6 inhibitors in its ability to more selectively target and inhibit CDK4."

The NEJM publication includes subgroup analyses according to line of therapy:

At 42 months, estimated survival rates among patients who received first-line therapy were 66.9% (95% CI, 58.7 to 73.9) with Kisqali plus fulvestrant vs. 56.3% (95% CI, 44.2 to 66.8) with fulvestrant alone (hazard ratio 0.70; 95% CI, 0.48 to 1.02)
Median overall survival among patients in the early-relapse and second-line subgroup was 40.2 months with Kisqali plus fulvestrant and 32.5 months with fulvestrant alone (hazard ratio, 0.73; 95% CI, 0.53 to 1.00)

A new post-hoc overall survival analysis based on prior endocrine therapy demonstrated that Kisqali plus fulvestrant had a:

36% reduction in risk of death in those who did not receive any previous endocrine therapy in any setting (HR= 0.64);
30% reduction in risk of death in those who were endocrine resistant, defined as progressive disease within the first 6 months of first-line endocrine therapy for advanced breast cancer while on endocrine therapy, or relapse within the first two years of (neo)adjuvant therapy (HR=0.70);
26% reduction in risk of death in those who were endocrine sensitive (HR=0.74).
No new safety signals were observed. The most common grade 3/4 adverse events of special interest observed in patients who received Kisqali plus fulvestrant compared to fulvestrant alone were neutropenia (57.1% vs 0.8%), hepatobiliary toxicity (13.7% vs 5.8%), QTc prolongation (3.1% vs 1.2%), respiratory disorders (2.3% vs 3.3%) and interstitial lung disease (0.2% vs 0%).

The publication of the full data results is available online.

About Kisqali (ribociclib)
Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)2.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Kisqali (ribociclib) Important Safety Information
KISQALI (ribociclib) is a prescription medicine used in combination with an aromatase inhibitor as the first hormonal-based therapy to treat pre/perimenopausal and postmenopausal women and in combination with fulvestrant as the first hormonal-based therapy or following disease progression on hormonal therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if KISQALI is safe and effective in children. KISQALI can cause severe or life-threatening inflammation of the lungs. Patients should tell their health care provider right away if they experience breathing problems or chest pains. KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. KISQALI is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. KISQALI can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking KISQALI and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking KISQALI, patients should tell their health care provider if they are pregnant, or plan to become pregnant as KISQALI can harm an unborn baby. Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with KISQALI. Patients should avoid grapefruit or grapefruit juice while taking KISQALI. The most common side effects (incidence ≥20%) include white blood cell count decreases, nausea, infections, tiredness, diarrhea, vomiting, hair loss, headache, constipation, rash, and cough. The most common grade 3/4 side effects (incidence >5%) were low neutrophils, low leukocytes, abnormal liver function tests, and low lymphocytes. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

APHINITY six-year results strengthen evidence of clinical benefit with Roche’s Perjeta-based regimen

On December 11, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY), the Breast International Group (BIG), Institut Jules Bordet Clinical Trials Support Unit (IJB-CTSU) and Frontier Science Foundation (FS) reported data from a second interim overall survival (OS) analysis of the phase III APHINITY study, evaluating the combination of Perjeta (pertuzumab), Herceptin (trastuzumab) and chemotherapy (the Perjeta-based regimen) as an adjuvant (after surgery) treatment for patients with HER2-positive early breast cancer (eBC) (Press release, Hoffmann-La Roche, DEC 11, 2019, View Source [SID1234552253]). This latest interim OS analysis was conducted after a median follow-up of approximately 74 months, compared to approximately 45 months for the primary analysis in 2017, and includes updated descriptive iDFS and cardiac safety data.1

"The goal of adjuvant treatment is to give each person with early breast cancer the best chance of a cure," said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "These new data with longer follow-up show the continued effect of the Perjeta-based regimen and an increased invasive disease-free survival benefit."

Martine Piccart, M.D., Ph.D., BIG co-founder and Scientific Director at Institut Jules Bordet, added: "These results demonstrate the importance of longer follow-up of APHINITY and further confirm the Perjeta-based regimen as the standard of care for people with HER2-positive early breast cancer at high risk of recurrence, such as those with lymph node-positive disease."

At this latest planned analysis, in the overall study population, the Perjeta-based regimen reduced the risk of breast cancer recurrence or death by 24%, compared to Herceptin, chemotherapy and placebo (HR=0.76; 95% CI 0.64-0.91). At six years, 90.6% of patients in the Perjeta arm have not seen their breast cancer return, compared to 87.8% in the placebo arm, an absolute benefit of 2.8%.1

Consistent with the primary analysis, the greatest effect continues to be observed in patients at high risk of recurrence, such as those with lymph node (LN)-positive disease. In these patients there was a 28% reduction in the risk of recurrence or death with the Perjeta-based regimen compared to Herceptin, chemotherapy and placebo (HR=0.72; 95% CI 0.59-0.87). This corresponds to an absolute improvement in iDFS at six years of 4.5% (87.9% vs. 83.4%). With longer follow-up, the treatment effect of the Perjeta-based regimen is seen regardless of hormone receptor (HR) status. The iDFS hazard ratio for HR-positive patients is 0.73 (95% CI 0.59-0.92). The iDFS hazard ratio for HR-negative patients is 0.83 (95% CI 0.63–1.10).1

Fewer deaths have been observed in the Perjeta-based regimen arm (125 vs. 147 [HR=0.85; 95% CI: 0.67-1.07]); however, data remain immature at this time. The APHINITY study continues as planned with the third interim analysis of OS scheduled for 2022. Continued follow-up of these patients is very important to determine a possible OS benefit.1

No new cardiac safety concerns emerged. The safety profile of the Perjeta-based regimen was consistent with that seen at primary analysis and in previous studies, with a low incidence of cardiac events. The percentage of primary cardiac events recorded in the Perjeta-based regimen arm was 0.8% vs. 0.3% in the placebo arm.1,2

Based on the primary study analysis in 2017, the clinical value of the Perjeta-based regimen for patients with HER2-positive eBC has been recognised by regulatory bodies around the world. This regimen is now approved for the treatment of eBC for people at a high risk of recurrence in more than 86 countries, including the US and across the EU. To date, more than 150,000 patients have been treated with the Perjeta-based regimen in this setting.3 The regimen has also been recognised in multiple international treatment guidelines, including those from St Gallen International Breast Cancer Conference, NCCN, ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper), which recommend it as an adjuvant standard treatment for patients with HER2-positive eBC at high risk of recurrence.4,5,6,7

These results from APHINITY will be presented in an oral session on Wednesday 11 December at 09.30 CT at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas, US, by Dr Martine Piccart (Abstract #GS1-04). The data will also be featured in SABCS’ official press programme.

About APHINITY
APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, phase III, randomised, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy, compared to Herceptin and chemotherapy, as adjuvant therapy in 4,805 people with operable HER2-positive eBC. The primary efficacy endpoint of the APHINITY study is iDFS, which in this study is defined as the time a patient lives without return of invasive breast cancer at any site, or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, OS, disease-free survival and health-related quality of life. The study will continue to follow participants for ten years.2,8

About Perjeta
Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or ‘dimerising’) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumour growth and survival.9 Binding of Perjeta to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different locations. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of HER signalling pathways, thus preventing tumour cell growth and survival.10

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and metastatic HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.11 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test which identifies people who will likely benefit from these medicines at the onset of their disease.

Trastuzumab deruxtecan achieved a tumour response rate of 60.9%
in pivotal Phase II HER2-positive metastatic breast cancer trial

On December 11, 2019 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) reported positive detailed data from the global pivotal Phase II single-arm DESTINY-Breast01 trial of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody drug conjugate (ADC) and potential new medicine, in patients with HER2-positive metastatic breast cancer who received two or more prior HER2-targeted regimens (Press release, AstraZeneca, DEC 11, 2019, View Source [SID1234552252]).

The primary endpoint of objective response rate (ORR), confirmed by independent central review, was 60.9% with trastuzumab deruxtecan monotherapy (5.4mg/kg). Patients had a median of six prior therapies for metastatic disease (2-27).

Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months and median progression-free survival (PFS) of 16.4 months. The median overall survival (OS) has not yet been reached, with an estimated survival rate of 86% at one year. The results were consistent across subgroups of patients.

José Baselga, Executive Vice President, Oncology R&D, said: "The clinically meaningful and durable responses seen among these patients illustrate the potential of trastuzumab deruxtecan to establish a new standard of care. These results are impressive, as women with this advanced stage of breast cancer have already endured multiple prior therapies for HER2-positive metastatic breast cancer."

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "The strength of the pivotal results and the consistency with previously reported trastuzumab deruxtecan data further underscore that this specifically engineered HER2-targeted antibody drug conjugate is delivering on its intent of enhancing efficacy for patients with HER2-positive metastatic breast cancer."

Ian E. Krop, a principal investigator of the DESTINY-Breast01 trial and Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, said: "These results are particularly striking as trastuzumab deruxtecan prompted a high level of durable tumour reduction among patients, the majority of whom had exhausted most if not all standard therapies for HER2-metastatic breast cancer. We are excited by these results and their potential to help patients with this advanced stage of breast cancer."

Summary of resultsi
Efficacy measure
Total evaluable (n=184) ii

ORR (%) (95% CI)
60.9 (53.4-68)
CR (%)
6.0
PR (%)
54.9
SD (%)
36.4
PD (%)
1.6
DCR (%) (95% CI)iii
97.3 (93.8-99.1)
CBR (%) (95% CI)iv
76.1 (69.3-82.1)
Median DoR (95% CI)
14.8 months (13.8-16.9)
Median PFS (95% CI)
16.4 months (12.7-NE)
Estimated OS at 12 months (%) (95% CI)
86 (80-91)
CI, confidence interval; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, not estimable.
i As assessed by independent central review.
ii 5.4mg/kg.
iii DCR is (CR + PR + SD)
iv CBR is (CR + PR + SD for ≥6 months)

The data were included as part of the press programme at the 2019 San Antonio Breast Cancer Symposium and simultaneously published online in The New England Journal of Medicine.

Prior therapies included trastuzumab emtansine (100%), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormone therapies (48.9%) and other systemic therapies (99.5%). Median treatment duration for trastuzumab deruxtecan was 10 months (0.7-20.5) with a median duration of follow-up of 11.1 months (0.7-19.9). As of data cut-off on 1 August 2019, 42.9% of patients remained on treatment.

The safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Breast01 was consistent with that observed in the Phase I trial. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (20.7%), anaemia (8.7%), nausea (7.6%), decreased white cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6.0%). Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment as determined by an independent review. The events were primarily Grade 1 or 2 (10.9%) in severity with one Grade 3 (0.5%) and no Grade 4 events. Four deaths (2.2%) were determined to be due to ILD.

Regulatory submission of trastuzumab deruxtecan for the treatment of patients with HER2-positive metastatic breast cancer was recently accepted with Priority Review by the US Food and Drug Administration. A regulatory submission has also been made to Japan’s Ministry of Health, Labour and Welfare.

About HER2-positive breast cancer
Approximately one in five breast cancers are HER2-positive.1,2 Despite recent improvements and approvals of new medicines, there remains significant unmet needs for patients with advanced HER2-positive metastatic breast cancer.3,4 This disease remains incurable with patients eventually progressing after currently available treatments.3,4

About HER2
HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poor prognosis in breast cancer patients.5 To be considered HER2-positive, tumour cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridisation (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.1 A finding of IHC 3+ and/or FISH amplification is considered positive.1

About DESTINY-Breast01
DESTINY-Breast01 is a pivotal Phase II, single-arm, open-label, global, multicentre, two-part trial evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with 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. Enrolment into DESTINY-Breast01 was completed in September 2018 with 184 patients at more than 100 sites globally.

About trastuzumab deruxtecan
Trastuzumab deruxtecan (DS-8201; fam-trastuzumab deruxtecan in the US only); is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced programme in AstraZeneca’s ADC scientific platform. 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.

A comprehensive development programme is underway in North America, Europe and Asia, including five pivotal trials in HER2-expressing metastatic breast and gastric cancers, including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II 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, are also underway.

About the collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise trastuzumab deruxtecan as a potential new medicine worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.