camizestrant (AZD9833)

Together with the clinical efficacy and manageable safety profile of camizestrant-CDK4/6i, and reduced risk of GHS/QoL deterioration, the PROs from the SERENA-6 trial support switching to this combination as a potential new treatment strategy to optimise and improve outcomes in patients with HR+/HER2- advanced breast cancer and ESR1m emergence, ahead of disease progression, during first-line AI-CDK4/6i.

P1, N=396, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2025 --> Dec 2026

P2, N=150, Not yet recruiting, MedSIR

The phase 3 SERENA-6 trial showed that, in ER+/HER2- advanced breast cancer patients with emerging ESR1 mutations in ctDNA during aromatase inhibitor (AI) plus CDK4/6 inhibitor therapy, switching the AI to camizestrant significantly improved progression-free survival and delayed quality-of-life (QoL) deterioration.1 However, the clinical utility of early ctDNA-guided switching remains unconfirmed, as secondary endpoints (including PFS2 and overall survival) are still immature.

P1, N=40, Completed, AstraZeneca | Recruiting --> Completed

P1/2, N=702, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Fulvestrant, the first selective estrogen receptor degrader (SERD) approved for clinical use, was developed to address this resistance and has remained the standard second-line endocrine therapy...The SERENA-6 trial demonstrated that early switching to the oral SERD camizestrant in patients with ESR1 mutation detected on ctDNA, prior to radiographic progression, significantly improved progression-free survival and patient-reported outcomes. However, whether molecular progression should routinely trigger treatment change remains an open question, requiring validation through long-term clinical endpoints. In conclusion, the integration of oral SERDs into current therapeutic algorithms poses clinical challenges, and ongoing trials will clarify their role across the disease continuum.

Camizestrant is well-tolerated, with anti-tumor activity in combination with CDK46i. These results support evaluation of camizestrant 75 mg plus standard CDK4/6i doses in Phase 3 trials.

P1, N=10, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jun 2025

ER is a clinically validated target, and when camizestrant was progressed into the clinic, the only approved SERD was fulvestrant which is delivered via once-monthly intramuscular injections. The analysis predicted broadly linear PK in humans at pharmacologically relevant doses. Despite uncertainty raised by the data in dogs, confidence in the predicted human PK profile, using human-relevant data, led to the progression of camizestrant to the clinical.

P1/2, N=804, Recruiting, AstraZeneca | Trial completion date: Mar 2027 --> Jun 2027 | Trial primary completion date: Mar 2027 --> Jun 2027

In patients with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.).