Business Wire

Datopotamab Deruxtecan Showed Encouraging and Durable Efficacy in Patients with Heavily Pretreated HR Positive, HER2 Low or Negative Metastatic Breast Cancer

Share

Initial results from the TROPION-PanTumor01 phase 1 trial of datopotamab deruxtecan (Dato-DXd) showed encouraging and durable efficacy in patients with heavily pretreated hormone receptor (HR) positive, HER2 low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridization [ISH]-) or HER2 negative (IHC 0) unresectable or metastatic breast cancer. Safety data were consistent with previous trials of datopotamab deruxtecan. Results were presented today as a Spotlight Poster Discussion (Abstract #PD13-08) at the 2022 San Antonio Breast Cancer Symposium (#SABCS22).

Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

Approximately 70% of breast cancer tumors are considered HR positive and HER2 low or negative.1 For patients with HR positive, HER2 low or negative metastatic breast cancer that progress on or are not suitable candidates for endocrine therapy, the current standard of care is single-agent chemotherapy.2

In this cohort of TROPION-PanTumor01 (n=41) where patients previously received a median of five lines of treatment for metastatic disease, datopotamab deruxtecan demonstrated an objective response rate (ORR) of 27% as assessed by blinded independent central review (BICR). All responses were partial (n=11) and 56% of patients achieved stable disease (n=23). The disease control rate (DCR) was 85% and median progression-free survival (PFS) was 8.3 months (95% confidence interval [CI]: 5.5-11.1). With median follow-up of 13.7 months (range, 9-16), the median duration of response (DoR; 95% CI: 4.4-NE) and the median overall survival (OS) had not been reached with 59% of patients alive for more than one year.

“Patients with HR positive, HER2 low or negative metastatic breast cancer who are not eligible for endocrine therapy or have exhausted treatment options have a poor prognosis,” said presenting author Funda Meric-Bernstam, MD, Chair of the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. “These preliminary results with datopotamab deruxtecan in patients with heavily pretreated HR positive, HER2 low or negative metastatic breast cancer are encouraging and warrant further evaluation in this setting.”

The safety profile of datopotamab deruxtecan was consistent with previous data with no new safety signals identified. The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were decreased lymphocyte count (15%), stomatitis (10%), anemia (7%), dyspnea (2%) and fatigue (2%). Serious TEAEs were observed in six (15%) patients, including one death due to dyspnea that was not considered treatment-related. Treatment discontinuations due to an adverse event occurred in five (12%) patients. No cases of grade 3 or higher diarrhea or febrile neutropenia were observed. One case of grade 3 interstitial lung disease was adjudicated as treatment-related.

“These results add to the growing body of data demonstrating the potential of datopotamab deruxtecan to treat certain types of metastatic breast cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “We look forward to the continued evaluation of our TROP2 directed antibody drug conjugate, including comparisons to standard therapy in earlier lines of treatment for HR positive, HER2 low or negative metastatic breast cancer through our ongoing TROPION-Breast01 phase 3 trial.”

“Many of these patients with metastatic breast cancer in TROPION-PanTumor01 had exhausted most of their available treatment options, having received a striking median of five prior regimens, including a CDK4/6 inhibitor for nearly all patients,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “These promising results with datopotamab deruxtecan in such a heavily pretreated patient population support our strong belief that this TROP2 directed antibody drug conjugate has the potential to improve outcomes for patients with HR positive, HER2 low or negative breast cancer in this, and possibly earlier settings.”

Patients in this cohort were heavily pretreated, receiving a median of five prior lines of treatment in the metastatic setting (range, 3-10). Prior treatments included CDK4/6 inhibitors (95%), capecitabine (83%), taxanes (59%), anthracyclines (54%), neoadjuvant chemotherapy (37%), mTOR inhibitors (29%) and PI3KCA inhibitors (20%). As of data cut-off on July 22, 2022, five patients remained on study treatment.

Summary of Results

Efficacy Measure

Datopotamab Deruxtecan (6 mg/kg)n=41

Confirmed ORR, %i,ii

27% (n=11)

PR, %

27% (n=11)

SD, %

56% (n=23)

Non-CR/non-PD, %

2% (n=1)

PD, %

12% (n=5)

NE, %

2% (n=1)

DCR, %i,iii

85% (n=35)

Median DoR (months) (95% CI)i

NE (4.4-NE)

Median PFS (months) (95% CI)i

8.3 months (5.5-11.1)

Median OS (months)

Not reached

CI, confidence interval; CR, clinical response; DCR, disease control rate; DoR, duration of response; NE, not evaluable; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease

i As assessed by BICR

ii ORR is (CR + PR)

iii DCR is (CR + PR + SD + non-CR/non-PD)

Daiichi Sankyo and AstraZeneca have a broad clinical development program for datopotamab deruxtecan in breast cancer, including the ongoing pivotal TROPION-Breast01 phase 3 trial evaluating datopotamab deruxtecan in patients with HR positive, HER2 low or negative, inoperable or metastatic breast cancer previously treated with chemotherapy.

About TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicenter phase 1 trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumors that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with non-small cell lung cancer (NSCLC) to assess the safety and efficacy of datopotamab deruxtecan to determine the recommended dose for expansion (6 mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, triple negative breast cancer (TNBC), HR positive, HER2 low or negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration-resistant prostate and esophageal cancer.

Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, time to response, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.

About HR Positive, HER2 Low or Negative Breast Cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.3 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.3

Breast cancer is considered HR positive, HER2 low or negative when the tumors test positive for estrogen and/or progesterone hormone receptors and low for HER2 (measured as a HER2 score of IHC 1+ or IHC 2+/ISH-) or negative for HER2 (measured as IHC 0).1,4 This subtype accounts for approximately 70% of diagnosed breast cancer cases and is associated with lower survival rates with 30% of patients anticipated to live beyond five years after diagnosis.1 Current standard of care treatment for patients with HR positive, HER2 low or negative metastatic breast cancer that progress on hormone therapy-based regimens is sequential single-agent chemotherapy, which is associated with a low median PFS of less than 10 months and OS of less than two years, underscoring the need for additional treatment options.2,5,6,7

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is broadly expressed in several types of solid tumors, including HR positive, HER2 low or negative breast cancer.8,9 TROP2 expression is an unfavorable prognostic factor for overall survival in all types of breast cancer.8

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of the three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.

A comprehensive development program called TROPION is underway globally with more than 10 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2 targetable tumors, including NSCLC, TNBC and HR positive, HER2 low or negative breast cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.

About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit: www.daiichisankyo.com.

References:

1 National Cancer Institute. SEER cancer stat facts: female breast cancer subtypes. Accessed December 2022.
2 NCCN Treatment Guidelines for Breast Cancer. Version 4.2022.
3 Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.
4 Iqbal N, et al. Mol Biol Int. 2014;852748.
5 Cortes J, et al. Lancet. 2011;377:914-923.
6 Yuan P, et al. Eur J Cancer. 2019;112:57-65.
7 Jerusalem G, et al. JAMA Oncol. 2018;4(10):1367–1374.
8Goldenberg D, et al. Oncotarget. 2018;9(48): 28989-29006.
9 Zaman S, et al. Onco Targets Ther. 2019;12:1781–1790.

To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.

Contact information

Media Contacts:

Global/US:
Rose Talarico
Daiichi Sankyo, Inc.
rtalarico@dsi.com
+1 973 775 0838 (mobile)

EU:
Simone Jendsch-Dowé
Daiichi Sankyo Europe GmbH
simone.dowe@daiichi-sankyo.eu
+49 (89) 78080 (office)

Japan:
Koji Ogiwara
Daiichi Sankyo Co., Ltd.
ogiwara.koji.ay@daiichisankyo.co.jp
+81 3 6225 1126 (office)

Investor Relations:
DaiichiSankyoIR@daiichisankyo.co.jp

About Business Wire

Business Wire
Business Wire



Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

Global Partners Announce Innovations for Marine Managers to Help Our Oceans With Private Sector Support From Mary Kay Inc.8.2.2023 18:03:00 CET | Press release

Ocean conservation managers and practitioners, global experts, and high-level officials are convening for the Fifth International Marine Protected Area Congress (IMPAC5) from February 3-9 in Vancouver, Canada, to take a stand to protect the ocean. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230208005180/en/ MPAth, short for Marine Protected Area Tool Hub, is a free online resource for seascape stakeholders at every level. It uses the same problem-solving matrix honed by marine experts to guide users through a learning journey and help them address their most pressing challenges on sustainable livelihoods, financing, effectiveness, and climate change. (Credit: UN Environment Programme) IMPAC5 is known as the preeminent conference for the exchange of knowledge within the global community of marine conservation managers, practitioners, and decision makers. It provides the opportunity to highlight the latest science and share

Morgan Stanley Hosts First Global Demo Day for Startups in Inclusive Ventures Lab8.2.2023 16:23:00 CET | Press release

Morgan Stanley (NYSE: MS) today is hosting its first global in-person Demo Day, with 10 participating companies from the US and Europe, the Middle East and Africa (EMEA). The cohort companies, all founded by women, will pitch over 200 investors, as well as potential business partners and customers. Over the past five months, Morgan Stanley’s Inclusive Ventures Lab has supported its eighth cohort of technology-enabled startups in the post-seed to Series A funding round stage, offering an intensive accelerator program designed to provide a variety of mentorship opportunities and business-growth resources from across the Firm’s network. “We are on a mission to change the investing landscape for underrepresented founders. Through our accelerator program we are providing promising startups with much-needed capital, the broad resources of Morgan Stanley and access to investors,” said Selma Bueno, Managing Director and Global Head of the Inclusive Ventures Group. “Today’s Demo Day showcases i

Dawex, Fraunhofer ISST and TNO Agree to co-Propose a Pre-Standardization Program on Trusted Data Transaction8.2.2023 16:00:00 CET | Press release

The French data exchange tech company Dawex, the German research organization Fraunhofer ISST and the Dutch research organization TNO, today announced they have reached an agreement to co-propose a workshop program from the European Committee for Standardization (CEN) on Trusted Data Transaction, initiating a standardization process. To tackle economic, environmental and societal challenges, public and private organizations, large corporations and SMBs are taking full advantage of the explosion of data, and are increasingly distributing, accessing and sharing data within emerging data ecosystems. Data transactions are expected to grow exponentially in the coming years, requiring clear frameworks to organize, simplify, and secure the exchange of data, in compliance with regulatory requirements. Trust is a cornerstone of data exchange as it cements the relationship and drives collaboration between all parties involved in the data transactions. To better understand the scope and implicati

DEWA is the first utility in the world to enrich its services with ChatGPT technology8.2.2023 15:54:00 CET | Press release

HE Saeed Mohammed Al Tayer, MD & CEO of Dubai Electricity and Water Authority (DEWA) announced that DEWA is working to enrich its services with ChatGPT technology supported by Microsoft. This will make DEWA the first utility globally and the first UAE government entity to use this new technology. This is part of DEWA’s continuous efforts to promote its leadership locally and globally. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230208005591/en/ DEWA is the first utility in the world to enrich its services with ChatGPT technology (Photo: AETOSWire) The announcement was made as HE Saeed Al Tayer received Naim Yazbeck, General Manager of Microsoft UAE. The move underlines DEWA’s pioneering successes in all digital areas and is a continuation of its use of Artificial Intelligence (AI), which started in 2017 by developing an AI roadmap. DEWA has already launched various services and initiatives that use AI to enrich the experi

Large Real-World, Multi-Center Study Demonstrates Viz.ai Platform Saves Critical Minutes in Stroke Care8.2.2023 15:15:00 CET | Press release

Viz.ai, the leader in AI-powered disease detection and care coordination, and TeleSpecialists LLC, a physician-owned management service organization committed to providing exceptional emergent and non-emergent neurology and psychiatric patient care via telemedicine, announced new data presented today at the International Stroke Conference (ISC) from the VALIDATE (Validation of Artificial intelligence to LImit Delays in Acute stroke Treatment and Endovascular therapy) study. The study demonstrated that hospital utilization of Viz’ AI-powered care coordination platform was associated with a 39.5 minute reduction in patient arrival to time of first contact with the neurointerventionalist for need for potential emergency endovascular treatment. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230208005564/en/ VALIDATE Study: Median Arrival to Neurointerventionalist Notification Times (Graphic: Business Wire) “In the world of strok

In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.

Visit our pressroom