Business Wire

Datopotamab Deruxtecan Showed Promising Responses as Monotherapy and in Combination with Durvalumab in Patients with Metastatic Triple Negative Breast Cancer in Two Early Trials

Share

Updated results from the TROPION-PanTumor01 phase 1 trial showed datopotamab deruxtecan (Dato-DXd) continued to demonstrate encouraging responses in patients with heavily pretreated metastatic triple negative breast cancer (TNBC) and disease progression following standard treatment. Results were presented today as a poster presentation (Abstract #P6-10-03) 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 15% of breast cancers are considered triple negative and are associated with higher disease recurrence and worse prognosis compared to other breast cancer subtypes.1,2 It is estimated that only 12% of patients with metastatic TNBC survive five years after diagnosis and median overall survival is between 12 to 18 months.1,3

In the TNBC cohort of TROPION-PanTumor01 (n=44) where patients previously received a median of three lines of treatment for metastatic disease, datopotamab deruxtecan demonstrated an objective response rate (ORR) of 32%, including one complete response (CR), 13 partial responses (PRs) and 18 cases of stable disease (SD) as assessed by blinded independent central review (BICR). In a subgroup of 27 patients who had not been previously treated with topoisomerase I inhibitor-based ADCs, the ORR was 44% including one CR, 11 PRs and 10 cases of SD. The median duration of response (DoR) was 16.8 months (95% confidence interval [CI]: 5.6-NE) across patient groups.

“Triple negative breast cancer is the most aggressive subtype of breast cancer with the average survival rate of less than 18 months for patients with pretreated metastatic disease,” said Aditya Bardia, MD, MPH, Director of Breast Cancer Research Program, Mass General Cancer Center and Associate Professor of Medicine at Harvard Medical School. “The durable tumor response and disease control seen with datopotamab deruxtecan in patients with pretreated triple negative breast cancer are encouraging, particularly in those patients who had not received previous treatment with topoisomerase I inhibitor-based antibody drug conjugate.”

In the overall cohort, datopotamab deruxtecan demonstrated median progression-free survival (PFS) of 4.4 months (95% CI: 3.0-7.3) and median overall survival (OS) of 13.5 months (95% CI: 10.1-16.3). In the subgroup of patients who had not been previously treated with a topoisomerase I inhibitor, median PFS and OS were 7.3 months (95% CI: 3.0-18.0) and 14.3 months (95% CI: 10.5-NE), respectively. The disease control rate (DCR) was consistent across the overall cohort and previously untreated subgroup at 80% and 81%, respectively.

The safety profile of datopotamab deruxtecan was consistent with previously reported data with no new safety signals identified. The most common grade 3 or higher treatment-emergent adverse events (TEAEs) were stomatitis (11%), decreased lymphocyte count (7%), fatigue (7%), vomiting (5%), anemia (2%), decreased neutrophil count (2%) and nausea (2%). Serious TEAEs were reported in nine patients (20.5%). Treatment discontinuations occurred in one patient (2%) due to grade 1 pneumonitis, which was adjudicated as not treatment-related interstitial lung disease (ILD). No cases of ILD were observed. No cases of febrile neutropenia or grade 3 or higher diarrhea were observed.

“Five-year survival rates for previously treated metastatic triple negative breast cancer are significantly lower than other subtypes of breast cancer, underscoring the need for new, durable therapies,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “We are working with urgency and care to evaluate datopotamab deruxtecan in multiple treatment settings in phase 3 trials, including the TROPION-Breast02 first-line phase 3 trial in patients with locally recurrent inoperable or metastatic triple negative breast cancer not candidates for anti-PD-L1 therapy.”

“The median duration of response of nearly 17 months seen in the TROPION-PanTumor01 trial in these patients reinforces the potential of datopotamab deruxtecan to treat this persistent disease,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “These results, along with the promising clinical response in combination with durvalumab seen in the BEGONIA trial, underscore the potential role of this TROP2 directed antibody drug conjugate for patients with triple negative breast cancer as both a monotherapy and in combinations.”

Patients in the TROPION-PanTumor01 trial were heavily pretreated, receiving a median of three prior regimens in the metastatic setting (range, 1-10). Prior treatments included taxanes (93%), anthracyclines (75%), capecitabine (61%), platinum-based chemotherapy (52%), immunotherapy (45%), topoisomerase I inhibitor-based ADCs (32%) and PARP inhibitors (18%). As of data cut-off on July 22, 2022, three patients remained on study treatment.

Summary of TROPION-PanTumor01 Results in Metastatic TNBC

Efficacy Measure

All TNBC Patients
[n=44 (6 mg/kg, n=42;
8 mg/kg, n=2)]

Patients Without Prior Topoisomerase I
Inhibitor-Based ADC
[n=27 (6 mg/kg, n=25; 8 mg/kg, n=2)]

Confirmed ORR, %i,ii

32% (n=14)

44% (n=12)

CR, %

2% (n=1)

4% (n=1)

PR, %

30% (n=13)

41% (n=11)

SD, %

41% (n=18)

37% (n=10)

Non-CR/non-PD, %

7% (n=3)

0

PD, %

18% (n=8)

15% (n=4)

NE, %

2% (n=1)

4% (n=1)

DCR, %i,iii

80% (n=35)

81% (n=22)

Median DoR (months) (95% CI)i

16.8 months (5.6-NE)

16.8 months (5.6-NE)

Median PFS (months) (95% CI)i

4.4 months (3.0-7.3)

7.3 months (3.0-18.0)

Median OS (months) (95% CI)

13.5 months (10.1-16.3)

14.3 months (10.5-NE)

CI, confidence interval; CR, complete 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

iAs assessed by BICR

iiORR is (CR + PR)

iiiDCR is (CR+PR+SD+non-CR/non-PD)

BEGONIA Arm 7 Updated Results
Updated results from the BEGONIA phase 1b/2 trial (n=61) showed datopotamab deruxtecan in combination with durvalumab, AstraZeneca’s immune checkpoint inhibitor, demonstrated an ORR of 73.6% (95% CI: 59.7-84.7) in patients with previously untreated unresectable, locally advanced or metastatic TNBC as assessed by investigator. Among the 53 evaluable patients, there were four CRs and 35 PRs. Responses were observed regardless of PD-L1 expression (low and high tumors) with 82% of patients continuing to respond at the time of data cut-off on July 22, 2022. These data were presented as a Spotlight Poster Discussion (abstract #PD11-09) at SABCS on December 8.

The safety profile of datopotamab deruxtecan in combination with durvalumab was consistent with the known safety profiles of both agents. The most common all-grade TEAEs occurring in 20% or more of patients were nausea (57.4%), stomatitis (55.7%), alopecia (45.9%), fatigue (39.3%), constipation (39.3%), rash (27.9%) and vomiting (21.3%). Serious TEAEs were observed in 10 (16.4%) patients. Treatment discontinuations due to an adverse event occurred in four patients (6.6%). Two (3.3%) cases were adjudicated as treatment-related grade 1 ILD.

Twenty-five patients (41.0%) had not received prior treatment for metastatic TNBC. Prior treatments for patients with disease progression following treatment for early-stage disease included radiotherapy (49.2%), anthracyclines (45.9%), taxanes (41.0%), platinum-based chemotherapy (14.8%), hormonal therapy (14.8%) and targeted therapy (4.9%). Seven (11.5%) patients had high PD-L1 expression (tumor area positivity [TAP]≥10%) and 53 patients (86.9%) had low PD-L1 expression (TAP<10%). At data cut-off, 45 patients remained on study treatment.

Daiichi Sankyo and AstraZeneca have a broad clinical development program for datopotamab deruxtecan in TNBC, including the recently initiated global TROPION-Breast03 phase 3 trial evaluating datopotamab deruxtecan with and without durvalumab in patients with stage 1 to 3 TNBC with residual disease after neoadjuvant therapy. The first patients were enrolled in November 2022 and are expected to be dosed in December 2022. SWOG Cancer Research Network Clinical Trials Partnerships (SWOG CTP) is the lead academic group for the trial and a key collaborator in its protocol development, US site selection and planned recruitment and analysis.

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, 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 BEGONIA
BEGONIA is an open-label, two-part, multicenter phase 1b/2 trial evaluating durvalumab in combination with oncology therapies with or without paclitaxel for the first-line treatment of metastatic TNBC. Arm 7 of the trial is evaluating the safety, tolerability and preliminary efficacy of datopotamab deruxtecan in combination with durvalumab in patients with previously untreated, unresectable locally advanced or metastatic TNBC.

The primary endpoints are safety and tolerability. The secondary endpoints include investigator-assessed ORR, PFS, DoR and OS.

About Triple Negative Breast Cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.4 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.4

Approximately 15% of breast cancers are considered triple negative, which is defined by tumors that test negative for estrogen and progesterone hormone receptors (HRs) and low or negative for human epidermal growth factor 2 receptor (HER2), as determined by an immunohistochemistry (IHC) test and/or an in-situ hybridization (ISH) test.1 Tumors with HER2 expression measured as IHC 0 are considered HER2 negative and tumors with HER2 expression measured as IHC 1+ or IHC 2+/ISH- are considered HER2 low.1,5 TNBC is considered the most aggressive subtype of breast cancer.1,2 Compared to patients with other breast cancer subtypes, the prognosis for patients with metastatic TNBC is generally worse with a five-year survival rate estimated at 12% and a median overall survival rate of 12 to 18 months.1,3

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is broadly expressed in several types of solid tumors, including approximately 80% of patients with TNBC.6,7,8 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 O’Reilly D, et al. World J Clin Oncol. 2021; 12(3):164-182.
3 Sharma P. et al. Oncologist. 2016;21(9):1050–1062.
4 Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.
5 Iqbal N, et al. Mol Biol Int. 2014;852748.
6 Goldenberg D, et al. Oncotarget. 2018;9(48): 28989-29006.
7 Ambrogi F, et al. PLoS One. 2014;9(5):e96993.
8 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

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 Contact:
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

More Than Half of Visitors to teamLab Planets in Toyosu, Tokyo Now Come From Overseas. Starting in March, Artworks Featuring Cherry Blossoms That Bloom Across the Space Will Be on View for the Spring Season Only27.1.2023 18:00:00 CET | Press release

Approximately 100,000 people from overseas visited teamLab Planets in Toyosu, Tokyo, between December 9, 2022 and January 9, 2023. (*1) Of the visitors across one month, around 60% , or 1 in 2 visitors, were non-residents visiting Japan (*1), and the number of visitors from overseas has tripled compared to the same month in 2019 (before COVID-19). This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230126005440/en/ teamLab, Floating in the Falling Universe of Flowers © teamLab Furthermore, according to a survey conducted by the museum, about 70% of the visitors from overseas knew about the museum before considering their trip to Japan, and there was a trend of the museum being one of the main purposes to visit Tokyo. (*2) *1 From the official website tickets purchaser data (survey period: December 9, 2022 - January 9, 2023) *2 From the visitor survey data (survey period: December 17, 2022 - January 10, 2023) We will continue to p

Global Processing Services Appoints Former Visa Executive Jim McCarthy to Lead Global Sales and Product27.1.2023 11:01:00 CET | Press release

Global Processing Services (“GPS”), a fast-growing next-gen global payments technology platform, today announced the appointment of Jim McCarthy as Executive Vice President – Global Head of Sales and Product, and Kevin Fox as the company’s new Chief Revenue Officer. In this newly created role, Jim will lead GPS’ global commercial and product teams in close collaboration with Kevin on sales acceleration. Jim is a highly accomplished payments veteran with over 30 years of experience, including 18 years at Visa where he held senior roles in sales, risk and authentication, consumer credit, digital products and product innovation. As Visa’s EVP of Innovation and Strategic Partnerships, Jim was responsible for the development of Visa’s product and technology roadmap, innovation efforts, and led business development for strategic partnerships. While at Visa he was responsible for the introduction of 3D Secure and Visa Token Service, which have become industry standards, and also contributed t

Major Landowner Federations to Support AMR Against Nordic Mining ASA (NOM) in the Norwegian Supreme Court27.1.2023 10:59:00 CET | Press release

Key landowner federations declare 3rd party intervention in support of Arctic Mineral Resources’ appeal to the Supreme Court in the case against Nordic Rutile AS (NRU), a wholly owned subsidiary of Nordic Mining ASA (NOM). Arnold Rørholt, lawyer and AMR’s Chairman, welcomes the 3rd party intervention in favour of AMR: “The intervention will ensure that the Supreme Court, as opposed to the courts of lower instance, appreciates the principal nature of the case and the Constitutional issues underpinning it, and interprets the Mineral Act in light of these – to the favour of AMR.” “The Western part of the Engebø garnet and rutile province contains around half of the proven reserves in the Engebø deposit, as well as a majority of inferred resources and will support a highly profitable 50 years plus fully underground mining project without a need for deposits on land or in the sea” continues Rørholt. Arctic Mineral Resources (AMR) and the federations argue that the two mineral categories – o

Ipsen Receives CHMP Negative Opinion for Palovarotene as a Treatment for Fibrodysplasia Ossificans Progressiva in E.U.27.1.2023 07:00:00 CET | Press release

Regulatory News: Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended not to grant marketing authorization for investigational palovarotene as a treatment for the ultra-rare bone disease, fibrodysplasia ossificans progressiva (FOP). In the E.U. there are currently only symptomatic treatments for FOP, which do not reduce the formation of extra-skeletal bone in patients with the condition. Ipsen will be requesting a re-examination of the CHMP opinion, based on scientific data available from the existing palovarotene clinical trial program. FOP causes permanent and continuous new bone formation in soft and connective tissues, like muscles, tendons and ligaments, a process known as heterotopic ossification (HO).1 Once formed, it is irreversible.1 The average age of diagnosis is 5 years old2 and ultimately FOP shortens the median life expectancy to 56 years as untimely death is

Green Steel Technology Company Boston Metal Announces $120M Series C Financing Led by ArcelorMittal27.1.2023 06:01:00 CET | Press release

Boston Metal, a company developing technology to fully decarbonize steel production, today announced the $120 million first close of Series C fundraising led by multinational steel company, ArcelorMittal S.A. (NYSE: MT). Microsoft's Climate Innovation Fund and SiteGround Capital also joined as new investors in this round, alongside current investors. ArcelorMittal’s lead investment was made through its XCarb® Innovation Fund. Commenting, Aditya Mittal, CEO, ArcelorMittal, said, “In Boston Metal, we are investing in a team that has made impressive progress over a relatively short period of time, developing a technology that has exciting potential to revolutionize steelmaking. In our extensive discussions with them, we have been impressed by the passion and vision they have to contribute to the decarbonization of steelmaking. They are an exciting and welcome addition to the XCarb® Innovation Fund’s portfolio.” Boston Metal’s patented Molten Oxide Electrolysis (MOE) process is being comme

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