Investigational Drug
Camizestrant
TrialFetch AI Analysis
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Overview
Camizestrant (AZD9833; AZ 14066724; UNII-JUP57A8EPZ) is an investigational, next‑generation, oral selective estrogen receptor degrader (SERD) and complete ER antagonist being developed for estrogen receptor–positive (ER+), HER2‑negative breast cancer. In October 2024, the randomized phase 2 SERENA‑2 trial reported significantly longer progression‑free survival (PFS) for camizestrant vs fulvestrant. In June 2025, the phase 3 SERENA‑6 trial showed a clinically meaningful PFS benefit when patients with emergent ESR1 mutations switched from an aromatase inhibitor (AI) to camizestrant while continuing their CDK4/6 inhibitor; the FDA granted Breakthrough Therapy designation based on these results. (thelancet.com)
Mechanism of action
- Small‑molecule oral SERD and complete ERα antagonist that degrades ER and blocks ER‑dependent transcription in both ESR1 wild‑type and ESR1‑mutant models, overcoming key endocrine‑resistance mechanisms. Preclinical data also support additive activity with CDK4/6 and PI3K/AKT/mTOR pathway inhibitors. (aacrjournals.org)
Efficacy
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Phase 3 (SERENA‑6; first‑line, ctDNA‑guided switch on emergent ESR1 mutation): Switching to camizestrant (75 mg daily) plus the same CDK4/6 inhibitor significantly prolonged PFS vs continuing AI plus CDK4/6 inhibitor (median 16.0 vs 9.2 months; HR 0.44, P<0.0001). Benefit was consistent across CDK4/6 partners and subgroups. Patient‑reported global health status and pain deterioration were also delayed (exploratory). Overall‑survival data were immature at the time of reporting. (biospace.com)
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Phase 2 (SERENA‑2; postmenopausal ER+/HER2− advanced disease after ≤1 prior endocrine therapy): Camizestrant improved investigator‑assessed PFS vs fulvestrant. Median PFS: 7.2 months (75 mg), 7.7 months (150 mg) vs 3.7 months (fulvestrant); HR 0.59 and 0.64, respectively. Objective response rate: 16%–17% (camizestrant) vs 12% (fulvestrant). In an exploratory analysis of patients with baseline ESR1 mutations, median PFS was 8.0 vs 2.2 months; HR 0.44. (thelancet.com)
Safety
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Class‑consistent and mostly low‑grade adverse events. In SERENA‑2, treatment‑related AEs occurred in 53% (75 mg) and 67% (150 mg) with camizestrant vs 18% with fulvestrant; grade ≥3 treatment‑related AEs were uncommon (≈1%–3%). Distinctive events with camizestrant included photopsia (any‑grade: ~12% at 75 mg; ~25% at 150 mg) and bradycardia, typically grade 1–2 and not leading to discontinuation. (thelancet.com)
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In SERENA‑6, safety of camizestrant plus CDK4/6 inhibitors aligned with known profiles; more neutropenia was observed in the camizestrant arm, likely reflecting longer CDK4/6 exposure; photopsia was reported but mainly mild. Discontinuations due to AEs were low (≈1%–2%). (ascopost.com)
Further reading
- Lancet Oncology (SERENA‑2 primary results). Camizestrant vs fulvestrant in ER+/HER2− advanced breast cancer. (thelancet.com)
- JCO abstract: SERENA‑2 ESR1‑mutant exploratory analysis. (ascopubs.org)
- NEJM (SERENA‑6): First‑line ctDNA‑guided switch to camizestrant plus CDK4/6 inhibitor on emergent ESR1 mutation. (ovid.com)
- Cancer Research (preclinical): Mechanism and combination rationale for camizestrant. (aacrjournals.org)
- ASCO Post summaries of SERENA‑6 and FDA Breakthrough designation. (ascopost.com)
Notes: Camizestrant remains investigational as of October 2025; regulatory status and overall‑survival outcomes are pending further updates from ongoing phase 3 programs. (medthority.com)
Last updated: Oct 2025
Active trials using Camizestrant
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with previously untreated ER-positive, HER2-negative unresectable locoregionally recurrent or metastatic breast cancer and ECOG 0–1 receive first-line camizestrant, an oral selective estrogen receptor degrader, plus the CDK4/6 inhibitor ribociclib. Pre/perimenopausal women and men without prior orchiectomy also receive ovarian or testicular suppression.
ClinicalTrials.gov ID: NCT07647328
TrialFetch AI summary: Adults with ER-positive/HER2-negative metastatic or locoregionally recurrent breast cancer progressing after prior systemic therapy including a CDK4/6 inhibitor receive oral camizestrant, an ER-degrading SERD, plus oral atirmociclib, a CDK4-selective cell-cycle inhibitor. Eligible patients have ECOG 0–1 and RECIST-assessable disease.
ClinicalTrials.gov ID: NCT07427394
TrialFetch AI summary: This trial enrolls adults with untreated, locally advanced or metastatic HR-positive, HER2-negative breast cancer and germline BRCA1, BRCA2, or PALB2 mutations, to compare saruparib (a PARP1-selective inhibitor) plus camizestrant (an oral SERD) versus physician's choice of CDK4/6 inhibitor plus endocrine therapy or plus camizestrant as first-line treatment.
ClinicalTrials.gov ID: NCT06380751
TrialFetch AI summary: Eligible patients are adult women with ER-positive, HER2-negative advanced breast cancer previously treated with CDK4/6 inhibitors or with metastatic high-grade serous ovarian cancer previously treated with platinum-based chemotherapy. The trial investigates AZD8421, an oral CDK2 inhibitor, as monotherapy or in combination with either camizestrant (oral SERD) or a CDK4/6 inhibitor.
ClinicalTrials.gov ID: NCT06188520
