Investigational Drug
Camizestrant
TrialFetch AI Analysis
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Overview
Camizestrant (AZD9833; AZ 14066724) is an oral, next-generation selective estrogen-receptor degrader (SERD) developed for estrogen receptor (ER)-positive breast cancer. It is no longer solely investigational in the United States: on September 4, 2026, the FDA granted accelerated approval under the brand name Etcamah, combined with a CDK4/6 inhibitor, for adults with HR-positive/HER2-negative locally advanced or metastatic breast cancer when an ESR1 mutation emerges during aromatase-inhibitor plus CDK4/6-inhibitor therapy. Continued approval depends on confirmation of clinical benefit. (fda.gov)
Mechanism of action
Camizestrant binds the ligand-binding domain of ERα, antagonizes signaling by both wild-type and mutant ESR1-encoded receptors, and induces proteasome-dependent ERα degradation without detectable agonist activity. Preclinical models showed activity against ER-positive tumors, including models resistant to endocrine or CDK4/6-inhibitor therapy. (accessdata.fda.gov)
Efficacy
In the phase III SERENA-6 trial, 315 patients whose tumors developed an ESR1 mutation during first-line aromatase-inhibitor plus CDK4/6-inhibitor treatment—before radiographic progression—were randomized either to switch the aromatase inhibitor to camizestrant 75 mg daily or continue their existing regimen. Median progression-free survival was 16.0 versus 9.2 months (hazard ratio 0.44; 95% CI 0.31–0.60; P<0.0001). Overall-survival data were immature. (nejm.org)
In the randomized phase II SERENA-2 trial after progression on endocrine therapy, median progression-free survival was 7.2 months with 75 mg and 7.7 months with 150 mg, versus 3.7 months with fulvestrant. Corresponding hazard ratios were 0.59 and 0.64. Objective responses occurred in approximately 16–17% of evaluable camizestrant-treated patients versus 12% with fulvestrant. (sciencedirect.com)
In the phase I SERENA-1 monotherapy study of heavily pretreated patients, the objective response rate across doses was 15.3%, the 24-week clinical-benefit rate was 35.2%, and median progression-free survival was 5.4 months. At 75 mg, these values were 18.8%, 54.2%, and 7.3 months, respectively. (annalsofoncology.org)
Safety
In SERENA-1 monotherapy, common treatment-related adverse events included visual effects (56%), sinus bradycardia (44%), fatigue (26%), and nausea (15%); most were grade 1–2, with no grade ≥3 treatment-related events at doses up to 150 mg. (pubmed.ncbi.nlm.nih.gov)
In SERENA-2, treatment-related adverse events occurred in 53% and 67% of patients receiving 75 mg and 150 mg, respectively, versus 18% with fulvestrant. No individual grade ≥3 treatment-emergent event affected more than 3% of any group, and there were no treatment-related deaths. (sciencedirect.com)
The US prescribing information carries a boxed warning for potentially serious arrhythmias when camizestrant is combined with QT-prolonging drugs, particularly ribociclib. Bradycardia, visual disturbances, fatigue, cytopenias and embryo-fetal toxicity are additional concerns. ECG, heart-rate and electrolyte monitoring are recommended. (accessdata.fda.gov)
Further reading
- SERENA-6 phase III trial — New England Journal of Medicine
- SERENA-2 phase II trial — The Lancet Oncology
- SERENA-1 monotherapy trial — Annals of Oncology
- Preclinical pharmacology — Clinical Cancer Research
- FDA accelerated-approval summary
- US prescribing information
Last updated: Sep 2026
Active trials using Camizestrant
Found 4 active trials using this drug:
TrialFetch AI summary: This single-arm study enrolls adults with unresectable recurrent or metastatic ER-positive, HER2-negative breast cancer who have received no systemic therapy for advanced disease. All receive first-line oral camizestrant, an estrogen-receptor degrader, plus ribociclib, a CDK4/6 inhibitor.
ClinicalTrials.gov ID: NCT07647328
TrialFetch AI summary: For patients with ER-positive, HER2-negative advanced or recurrent breast cancer that has progressed after systemic therapy, with prior CDK4/6-inhibitor exposure and ECOG performance status 0–1, this single-arm study evaluates camizestrant, an oral estrogen-receptor degrader, plus atirmociclib, an oral selective CDK4 inhibitor. Patients receive a single atirmociclib dose before starting the combination.
ClinicalTrials.gov ID: NCT07427394
TrialFetch AI summary: Adults with previously untreated unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer and a germline BRCA1, BRCA2, or PALB2 loss-of-function mutation are randomized to saruparib, a selective PARP1 inhibitor, plus camizestrant, an estrogen-receptor degrader; physician-selected CDK4/6 inhibition plus standard endocrine therapy; or CDK4/6 inhibition plus camizestrant.
ClinicalTrials.gov ID: NCT06380751
TrialFetch AI summary: Women with progressing advanced or metastatic ER-positive/HER2-negative breast cancer previously treated with a CDK4/6 inhibitor, or platinum-treated metastatic high-grade serous ovarian cancer, may receive AZD8421, an investigational selective CDK2 inhibitor, as monotherapy. In the breast cancer cohorts, AZD8421 is also studied with camizestrant and palbociclib, abemaciclib, or ribociclib.
ClinicalTrials.gov ID: NCT06188520
