23 September 2024
Datopotamab deruxtecan final
overall survival results reported in
patients with metastatic
HR-positive, HER2-low or negative breast cancer
in
TROPION-Breast01 Phase III
trial
Survival results for
AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan in
TROPION-Breast01 did not achieve statistical significance versus
chemotherapy
Trial previously met the dual
primary
endpoint of progression-free
survival
High-level results from the
TROPION-Breast01 Phase III trial of datopotamab deruxtecan
(Dato-DXd) compared to investigator's choice of chemotherapy, which
previously met the dual primary endpoint of progression-free
survival (PFS), did not achieve statistical significance in the
final overall survival (OS) analysis in patients with inoperable or
metastatic hormone receptor (HR)-positive, HER2-low or negative
(IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated
with endocrine-based therapy and at least one systemic
therapy.
This analysis follows the positive
PFS results
presented at the 2023 European Society
for Medical Oncology Congress which showed datopotamab deruxtecan
demonstrated a statistically significant and clinically meaningful
improvement in PFS. An improvement in patient-reported outcomes was
also seen.1 The PFS data and additional results for key
secondary endpoints were published
this month in the Journal of Clinical
Oncology.
The safety profile of datopotamab
deruxtecan was consistent with that observed in the previous
analysis including lower rates of Grade 3 or higher
treatment-related adverse events compared to chemotherapy, and no
new safety concerns identified. All grade interstitial lung disease
(ILD) rates remained low with no new Grade
3 or higher ILD events observed.
With multiple antibody drug
conjugates (ADCs) approved during the course of the trial,
including Enhertu
(trastuzumab deruxtecan), subsequent treatment following patients'
disease progression or treatment discontinuation is likely to have
affected survival results.
Susan Galbraith, Executive Vice
President, Oncology R&D, AstraZeneca, said: "The metastatic
HR-positive breast cancer treatment landscape has advanced
remarkably in the last several years to the benefit of patients.
Based on the TROPION-Breast01 results, there is evidence of the
clinical value of datopotamab deruxtecan in this setting. We will
continue discussions with regulatory authorities and apply insights
from these results to our clinical development programme for
datopotamab deruxtecan in breast cancer."
Ken Takeshita, MD, Global Head,
R&D, Daiichi Sankyo, said: "Datopotamab deruxtecan has
previously shown a statistically significant progression-free
survival benefit in TROPION-Breast01, a result supported by
multiple meaningful secondary measures including patient-reported
outcomes. We are proud to have brought forth a new standard of care
for patients with metastatic breast cancer with Enhertu and we remain committed to
making datopotamab deruxtecan another potential option for patients
who can benefit."
Datopotamab deruxtecan is a
specifically engineered TROP2-directed DXd ADC discovered by
Daiichi Sankyo and being jointly developed by AstraZeneca and
Daiichi Sankyo.
The data will be presented at a
forthcoming medical meeting and shared with regulatory authorities
currently reviewing applications for this indication.
In addition to TROPION-Breast01,
AstraZeneca and Daiichi Sankyo are evaluating datopotamab
deruxtecan alone and with immunotherapy as treatment for patients
with triple-negative or HR-low, HER2-negative breast cancers in
the TROPION-Breast02,
TROPION-Breast03,
TROPION-Breast04
and TROPION-Breast05
Phase III trials.
Notes
HR-positive breast cancer
Breast cancer is the second most
common cancer and one of the leading causes of cancer-related
deaths worldwide.2 More than two million breast cancer
cases were diagnosed in 2022 with more than 665,000 deaths
globally.2 While survival rates are high for those
diagnosed with early breast cancer, less than 35% of patients
diagnosed with or who progress to metastatic disease are expected
to live five years following diagnosis.3
Approximately 70% of diagnosed cases
are considered what has been historically called HR-positive,
HER2-negative breast cancer (measured as HER2 score of IHC 0, IHC
1+ or IHC 2+/ISH-).3 Endocrine therapies are widely
given consecutively in the early lines of treatment for HR-positive
metastatic breast cancer; however, after two lines of treatment,
further efficacy from endocrine therapy is often
limited.4 The current standard of care following
endocrine therapy is chemotherapy, which is associated with poor
response rates and outcomes.4-7
TROP2 is a protein broadly expressed
in HR-positive, HER2-negative breast cancer and is associated with
increased tumour progression and poor
survival.8,9
TROPION-Breast01
TROPION-Breast01 is a global, randomised, multicentre,
open-label Phase III trial evaluating the efficacy and safety of
datopotamab deruxtecan (6.0mg/kg) versus investigator's choice of
single-agent chemotherapy (eribulin, capecitabine, vinorelbine or
gemcitabine) in adult patients with unresectable or metastatic
HR-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-)
breast cancer who have progressed on and are not suitable for
endocrine therapy per investigator assessment and have received at
least one additional systemic therapy for unresectable or
metastatic disease.
Following disease progression or
discontinuation of datopotamab deruxtecan or chemotherapy, patients
had the option to receive subsequent treatment at the discretion of
their physician. Crossover between trial arms was not
permitted.
The dual primary endpoints of
TROPION-Breast01 are PFS as assessed by blinded independent central
review and OS. Key secondary endpoints include objective response
rate, duration of response, investigator-assessed PFS, disease
control rate, time to first subsequent therapy and
safety.
TROPION-Breast01 enrolled more than
700 patients in Africa, Asia, Europe, North America and South
America. For more information visit ClinicalTrials.gov.
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 six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and
one of the most advanced programmes in AstraZeneca's ADC scientific
platform. Datopotamab deruxtecan is comprised of a humanised
anti-TROP2 IgG1 monoclonal antibody, developed in collaboration
with Sapporo Medical University, attached to a number of
topoisomerase I inhibitor payloads (an exatecan derivative, DXd)
via tetrapeptide-based cleavable linkers.
A comprehensive global clinical
development programme is underway with more than 20 trials
evaluating the efficacy and safety of datopotamab deruxtecan across
multiple cancers, including NSCLC, triple-negative breast cancer
(TNBC) and HR-positive, HER2-negative breast
cancer. The programme includes seven
Phase III trials in lung cancer and five Phase III trials in breast
cancer evaluating datopotamab deruxtecan as a monotherapy and in
combination with other anticancer treatments in various
settings.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo
entered into a global collaboration to jointly develop and
commercialise Enhertu
in
March 2019 and datopotamab deruxtecan
in
July 2020, except in Japan where
Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi
Sankyo is responsible for the manufacturing and supply of
Enhertu and datopotamab
deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding
of breast cancer biology, AstraZeneca is starting to challenge, and
redefine, the current clinical paradigm for how breast cancer is
classified and treated to deliver even more effective treatments to
patients in need - with the bold ambition to one day eliminate
breast cancer as a cause of death.
AstraZeneca has a comprehensive
portfolio of approved and promising compounds in development that
leverage different mechanisms of action to address the biologically
diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a
HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to
improve outcomes in previously treated HER2-positive and HER2-low
metastatic breast cancer and are exploring its potential in earlier
lines of treatment and in new breast cancer settings.
In HR-positive breast cancer,
AstraZeneca continues to improve outcomes with foundational
medicines Faslodex and
Zoladex (goserelin) and
aims to reshape the HR-positive space with first-in-class AKT
inhibitor, Truqap, and
next-generation SERD and potential new medicine camizestrant.
AstraZeneca is also collaborating with Daiichi Sankyo to explore
the potential of TROP2-directed ADC, datopotamab deruxtecan, in
this setting.
PARP inhibitor Lynparza (olaparib) is a targeted
treatment option that has been studied in early and metastatic
breast cancer patients with an inherited BRCA mutation. AstraZeneca
with MSD (Merck & Co., Inc. in the US and Canada) continue to
research Lynparza in these
settings and to explore its potential in earlier
disease.
To bring much-needed treatment
options to patients with TNBC, an aggressive form of breast cancer,
AstraZeneca is evaluating the potential of datopotamab deruxtecan
alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with
chemotherapy, and Imfinzi
in combination with other oncology medicines, including
Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution
in oncology with the ambition to provide cures for cancer in every
form, following the science to understand cancer and all its
complexities to discover, develop and deliver life-changing
medicines to patients.
The Company's focus is on some of
the most challenging cancers. It is through persistent innovation
that AstraZeneca has built one of the most diverse portfolios and
pipelines in the industry, with the potential to catalyse changes
in the practice of medicine and transform the patient
experience.
AstraZeneca has the vision to
redefine cancer care and, one day, eliminate cancer as a cause of
death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global,
science-led biopharmaceutical company that focuses on the
discovery, development, and commercialisation of prescription
medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory
& Immunology. Based in Cambridge, UK, AstraZeneca's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com
and follow the Company on social media @AstraZeneca.
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References
1. Pernas S, et al. Datopotamab deruxtecan
(Dato-DXd) vs chemotherapy in previously-treated inoperable or
metastatic hormone receptor-positive, HER2-negative (HR+/HER2-)
breast cancer: Patient-reported outcomes (PROs) from the
TROPION-Breast01 study. Presented at: ASCO Congress 2024; 31 May -
4 June, 2024; Chicago, IL. Abstract 1006.
2. Bray F, et al. Global cancer statistics 2022:
GLOBOCAN estimates of incidence and mortality worldwide for 36
cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi:
10.3322/caac.21834.
3. National Cancer Institute. Surveillance,
Epidemiology and End Results Program. Available
at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed August 2024
4. Manohar P, et al. Updates in endocrine therapy
for metastatic breast cancer. Cancer Biol Med. 2022 Feb 15;
19(2):202-212.
5. Cortes J, et al. Eribulin monotherapy
versus treatment of physician's choice in patients with metastatic
breast cancer (EMBRACE): a phase 3 open-label randomised
study. Lancet. 2011;377:914-923.
6. Yuan P, et al. Eribulin mesilate versus
vinorelbine in women with locally recurrent or metastatic breast
cancer: A randomised clinical trial. Eur J Cancer.
2019;112:57-65.
7. Jerusalem G, et al. Everolimus Plus Exemestane
vs Everolimus or Capecitabine Monotherapy for Estrogen
Receptor-Positive, HER2-Negative Advanced Breast
Cancer. JAMA Oncol.
2018;4(10):1367-1374.
8. Goldenberg D, et al. The emergence of
trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer
target. Oncotarget. 2018;9(48): 28989-29006.
9. Vidula N, et al. Trophoblast
Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast
cancer. Breast Cancer Res
Treat. 2022 Aug;194(3):569-575.
Adrian Kemp
Company
Secretary
AstraZeneca
PLC