REG - AstraZeneca PLC - Final OS results reported for TROPION-Breast01

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RNS Number : 1374F  AstraZeneca PLC  23 September 2024

 

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
(https://www.daiichisankyo.com/files/news/pressrelease/pdf/202310/20231023_E2.pdf)
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 (https://ascopubs.org/doi/10.1200/JCO.24.00920) 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 (https://clinicaltrials.gov/study/NCT05374512) ,
TROPION-Breast03 (https://www.clinicaltrials.gov/study/NCT05629585) ,
TROPION-Breast04 (https://clinicaltrials.gov/study/NCT06112379) and
TROPION-Breast05 (https://clinicaltrials.gov/study/NCT06103864) 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
(https://clinicaltrials.gov/study/NCT05104866) .

 

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
(https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html#modal-historic-confirmation)
and datopotamab deruxtecan in July 2020
(https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-daiichi-sankyo-enter-collaboration-to-develop-and-commercialise-new-antibody-drug-conjugate.html#modal-historic-confirmation)
, 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 (https://www.astrazeneca.com/) .com and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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
(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

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