REG - AstraZeneca PLC - FDA ODAC vote on camizestrant in breast cancer

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RNS Number : 6967C  AstraZeneca PLC  01 May 2026

01 May 2026

Update on FDA Advisory Committee vote on camizestrant in combination with a
CDK4/6 inhibitor for advanced HR-positive breast cancer

The US Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee
(ODAC) did not reach a majority vote in favor of the benefit risk profile of
AstraZeneca's camizestrant in combination with a cyclin-dependent kinase (CDK)
4/6 inhibitor (palbociclib, ribociclib or abemaciclib) for the 1st-line
treatment of patients with hormone receptor (HR)-positive, HER2-negative
advanced breast cancer whose tumours have an emergent ESR1 mutation, based on
the SERENA-6 Phase III trial. The Committee voted 3 to 6.

 

In July 2025, the FDA accepted the New Drug Application (NDA) for camizestrant
in combination with a CDK4/6 inhibitor based on positive results from the
pivotal SERENA-6 Phase III trial presented at the 2025 American Society of
Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The
New England Journal of Medicine (https://www.nejm.org/) .(1) The FDA granted
Breakthrough Therapy Designation (BTD) for the camizestrant combination in
this setting in May 2025.

 

The FDA is not bound by the Committee's guidance but takes its advice into
consideration. AstraZeneca will continue to work with the FDA as it completes
its review of the application.

 

Kevin Kalinsky, MD, MS, FASCO, Division Director of Medical Oncology, Winship
Cancer Institute of Emory University and investigator for the trial, said:
"Patients with this specific form of breast cancer are in urgent need of new
treatments that delay disease progression. Today's recommendation by the ODAC
is disappointing, as new options and innovative treatment strategies which
address emerging resistance ahead of disease progression and deterioration in
quality of life are needed in the 1st-line setting."

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "New innovations and novel treatment strategies that
provide benefit to patients are required to drive advances in this 1st-line
setting, and so we are disappointed with the mixed outcome of today's ODAC
meeting. We strongly believe in the results of the SERENA-6 trial, and are
encouraged that the Committee saw camizestrant as a safe and effective
potential new medicine. We remain confident in the clinical benefit the
combination can bring to patients by changing therapeutic strategy at the
earliest opportunity, and are committed to challenging the status quo in the
pursuit of innovation that optimises outcomes for patients."

 

Results from a planned interim analysis of the SERENA-6 Phase III trial showed
a highly statistically significant and clinically meaningful 56% reduction in
the risk of disease progression or death with the camizestrant combination
versus standard-of-care treatment with an aromatase inhibitor (AI)
(anastrozole or letrozole) in combination with a CDK4/6 inhibitor (based on a
hazard ratio  HR  of 0.44; 95% confidence interval  CI  0.31-0.60;
p<0.00001).(1) Median PFS was 16.0 months for patients who switched to the
camizestrant combination versus 9.2 months for the comparator arm, and nearly
one third (29.7%) of patients in the camizestrant arm showed sustained disease
control at 24 months of treatment, versus 5.4% patients in the AI arm.(1)

Data for the key secondary endpoints of time to second disease progression
(PFS2) and overall survival (OS) were immature at the time of the interim
analysis, however a subsequent pre-planned analysis demonstrated a
statistically significant and clinically meaningful PFS2 benefit of 25.7
months versus 19.1 months in favour of the camizestrant combination (HR: 0.63;
95% CI: 0.46, 0.86; p = 0.00373) and OS continued to mature in favour of the
camizestrant combination (HR: 0.87, CI: 0.57-1.30). The trial will continue to
assess OS as a key secondary endpoint. Additional analyses of patient reported
outcome (PRO) measures published in Annals of Oncology
(https://www.annalsofoncology.org/) showed that the camizestrant combination
demonstrated consistent benefit in delaying time to deterioration (TTD) in
quality of life and reduced the risk of deterioration in patient-reported
cancer symptoms and functioning, where the camizestrant combination reduced
the risk of deterioration in global health status and quality of life by 46%
compared with the AI combination (HR 0.54; 95% CI, 0.34-0.84; nominal
p<0.001).(2)

The safety profile of camizestrant in combination with palbociclib, ribociclib
or abemaciclib in the SERENA-6 trial was consistent with the known safety
profile of each medicine. No new safety concerns were identified and
discontinuations were very low and similar in both arms.

 

SERENA-6 is the first global, double-blind, registrational Phase III trial to
use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence
of endocrine resistance and inform a switch in therapy before disease
progression. The innovative trial design used ctDNA monitoring via a blood
test at the time of routine tumour scans every two to three months to identify
patients for early signs of endocrine resistance via the emergence of ESR1
mutations. Following detection of an ESR1 mutation without disease
progression, the endocrine therapy of patients was switched to camizestrant
from ongoing treatment with an AI, while continuing combination with the same
CDK4/6 inhibitor.

 

Regulatory applications for camizestrant in this setting are also under review
in the EU, Japan and several other countries.

 

 

Notes

 

HR-positive breast cancer

Breast cancer is the second most common cancer and one of the leading causes
of cancer-related deaths worldwide.(3 )More than two million patients were
diagnosed with breast cancer in 2022, with more than 665,000 deaths
globally.(3) In the US,( )breast cancer is the most common cancer in women,
with more than 300,000 new cases of the disease diagnosed annually, and more
than 42,000 deaths.(4) While survival rates are high for those diagnosed with
early breast cancer, only about 30% of patients diagnosed with or who progress
to metastatic disease are expected to live five years following
diagnosis.(5)

 

HR-positive breast cancer, characterised by the expression of estrogen or
progesterone receptors, or both, is the most common subtype of breast cancer
with 70% of tumours considered HR-positive and HER2-negative.(5) Estrogen
receptor (ERs) often drive the growth of HR-positive breast cancer cells.(6)

 

Globally, approximately 200,000 patients with HR-positive breast cancer are
treated with a medicine in the 1st-line setting; most frequently with
endocrine therapies that target ER-driven disease, which are often paired with
CDK4/6 inhibitors.(7-9) In the US, approximately 37,000 patients with
HR-positive metastatic breast cancer are treated with these therapies in the
1st-line setting.(7-9) However, resistance to these therapies develops in many
patients.(9) Once this occurs, treatment options are limited and survival
rates are low with approximately 36% of patients anticipated to live beyond
five years after diagnosis.(5,9)

 

Mutations in the ESR1 gene are a key driver of endocrine resistance and are
associated with poor outcomes, emerging during treatment of the disease and
becoming more prevalent as the disease progresses.(10,11) Approximately 30% of
patients with endocrine sensitive HR-positive disease develop ESR1 mutations
during 1st-line treatment before disease progression.(7)

 

The optimisation of endocrine therapy and overcoming resistance to enable
patients to continue benefiting from these treatments, as well
as identifying new therapies for those who are less likely to benefit, are
active areas of focus for breast cancer research.

 

SERENA-6

SERENA-6 is a Phase III, double-blind, randomised trial evaluating the
efficacy and safety of camizestrant in combination with a CDK4/6 inhibitor
(palbociclib, ribociclib or abemaciclib) versus treatment with an AI
(anastrozole or letrozole) in combination with a CDK4/6 inhibitor
(palbociclib, ribociclib or abemaciclib) in patients with HR-positive,
HER2-negative advanced breast cancer (patients with either locally advanced
disease, or metastatic disease) whose tumours have an emergent ESR1 mutation.

 

The global trial enrolled 315 adult patients with histologically confirmed
HR-positive, HER2-negative advanced breast cancer, undergoing treatment with
an AI in combination with a CDK4/6 inhibitor as 1st-line treatment. The
primary endpoint of the SERENA-6 trial is PFS as assessed by investigator,
with secondary endpoints including OS, and PFS2 by investigator assessment.

 

Camizestrant

Camizestrant is an investigational, potent, next-generation oral selective
estrogen receptor degrader (SERD) and complete ER antagonist that is currently
in Phase III trials for the treatment of HR-positive breast cancer.

 

AstraZeneca's broad, robust and innovative clinical development programme,
including the SERENA-6, SERENA-4, CAMBRIA-1 and CAMBRIA-2 trials, is
evaluating the safety and efficacy of camizestrant when used as a monotherapy
or in combination with CDK4/6 inhibitors to address a number of areas of unmet
need in HR-positive, HER2-negative breast cancer.

 

Camizestrant has demonstrated anti-cancer activity across a range of
preclinical models, including those with ER-activating mutations. In the
SERENA-2 Phase II trial, camizestrant demonstrated a statistically significant
and clinically meaningful improvement in PFS versus Faslodex (fulvestrant) in
the overall trial population, including in patients with ESR1 tumour mutations
irrespective of prior treatment with CDK4/6 inhibitors in patients with
ER-positive locally advanced or metastatic breast cancer, previously treated
with endocrine therapy. The SERENA-1 Phase I trial demonstrated that
camizestrant is well tolerated and has a promising anti-tumour profile when
administered alone or in combination with palbociclib, ribociclib and
abemaciclib; three widely used CDK4/6 inhibitors.

 

AstraZeneca in breast cancer

Driven by a growing understanding of breast cancer biology, AstraZeneca is
challenging, and redefining, 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 antibody drug
conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes
in previously treated HER2-positive, HER2-low and HER2-ultralow 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, the
TROP-2-directed ADC, Datroway (datopotamab deruxtecan) and next-generation
oral SERD and potential new medicine camizestrant.

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. AstraZeneca is also
exploring the potential of saruparib, a potent and selective inhibitor of
PARP1, in combination with camizestrant in BRCA-mutated, HR-positive,
HER2-negative advanced breast cancer.

To bring much-needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with
Daiichi Sankyo to evaluate the potential of Datroway alone and in combination
with immunotherapy Imfinzi (durvalumab).

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 (https://www.astrazeneca.com/)

AstraZeneca (LSE/STO/NYSE: 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 (http://www.astrazeneca.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
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.

 

References

1.   Bidard FC, et al. First-Line Camizestrant for Emerging ESR1-Mutated
Advanced Breast Cancer. N Engl J Med 2025; DOI: 10.1056/NEJMoa2502929.

2.   Mayer E, et al. Patient-reported outcomes in the SERENA-6 trial of
camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and
emergent ESR1 mutations during first-line endocrine-based therapy. Ann Oncol
2026; 37(2):180-193.

3.   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; 1- 35. DOI:10.3322/caac.21834.

4.   American Cancer Society. Key Statistics for Breast Cancer. Available
at:
https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html
(https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html)
. Accessed April 2026.

5.   National Cancer Institute. Cancer Stat facts: Female breast cancer
subtypes. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(https://seer.cancer.gov/statfacts/html/breast-subtypes.html) . Accessed April
2026.

6.   Scabia V, et al. Estrogen receptor positive breast cancers have patient
specific hormone sensitivities and rely on progesterone receptor. Nat Commun.
2022; 10.1038/s41467-022-30898-0.

7.   Cerner CancerMPact database. Accessed April 2026.

8.   Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus
Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive,
HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.

9.   Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in
Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging
Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30.

10.  Brett O, et al. ESR1 mutation as an emerging clinical biomarker in
metastatic hormone receptor‑positive breast cancer. Breast Cancer Res. 2021;
23:85.

11.  Zundelevich A, et al. ESR1 mutations are frequent in newly diagnosed
metastatic and loco-regional recurrence of endocrine-treated breast cancer and
carry worse prognosis. Breast Cancer Res. 2020; 22:16.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

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