Etcamah (camizestrant) / AstraZeneca - LARVOL DELTA

CARA: Phase II Study of CAmizestrant in Resectable Endometrial Adenocarcinoma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University Health Network, Toronto

New P2 trial • Endometrial Adenocarcinoma • Endometrial Cancer • Oncology • Solid Tumor • ER • TP53

Camizestrant: First Approval. (PubMed, Drugs) - "In patients with ER-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer with a detectable ESR1 mutation, switching to camizestrant while continuing the same CDK4/6 inhibitor significantly prolonged progression-free survival in comparison with continuing treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. This article summarizes the milestones in the development of camizestrant leading to this first approval for the treatment of adults with locally advanced or metastatic hormone receptor positive (HR+), HER2-negative breast cancer with an ESR1 gene mutation that emerges during first-line hormonal therapy, in combination with CDK4/6 inhibitors."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Visual functioning and characterization of visual effects from SERENA-6, a Phase 3 study of switch to camizestrant (CAMI) from aromatase inhibitor (AI) while continuing CDK4/6 inhibitor (CDK4/6i) at emergence of ESR1 mutations (ESR1m) during first-line therapy for patients (pts) with HR+/HER2− advanced breast cancer (ABC) (SABCS 2025) - "Visual effects reported with CAMI + CDK4/6i were mostly low grade and occurred early in treatment. Together with the clinical efficacy and well-tolerated safety profile of CAMI + CDK4/6i, these data support this combination as a potential new treatment strategy for pts with HR+/HER2− ABC and emergent ESR1m during first-line AI + CDK4/6i."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Oral selective estrogen receptor degraders in ER+/HER2- breast cancer: a systematic review with pooled analysis of metastatic randomized trials and narrative synthesis of adjuvant evidence. (PubMed, Front Oncol) - "We searched PubMed, Cochrane CENTRAL, and conference abstract archives (SABCS, ESMO, ASCO; 2020-2026) for Phase II/III randomized controlled trials comparing oral SERDs (giredestrant, imlunestrant, elacestrant, camizestrant, vepdegestrant, amcenestrant) with standard endocrine therapy in ER-positive, HER2-negative breast cancer. This evidence synthesis across the full breast cancer continuum offers a framework for clinical decision-making as oral SERDs expand from advanced to early-stage disease. https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD420261358420."

Journal • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ER • HER-2

CAMBRIA-1 & CAMBRIA-2 phase III trials: camizestrant versus standard endocrine therapy in ER+/HER2- early breast cancer. (PubMed, Future Oncol) - P3 | "CAMBRIA-1 and CAMBRIA-2 are comparing the next-generation oral SERD camizestrant versus standard-of-care endocrine therapy (aromatase inhibitors or tamoxifen) in patients with ER-positive/HER2-negative early breast cancer, who are at intermediate or high risk of disease recurrence...CAMBRIA-2 is comparing 7 years of upfront adjuvant camizestrant versus endocrine therapy, with abemaciclib permitted in both treatment arms for the first 2 years. The primary endpoint for both studies is invasive breast cancer-free survival. Secondary endpoints include invasive disease-free survival, distant recurrence-free survival, overall survival, pharmacokinetics, patient-reported outcomes, safety and tolerability.Tweetable abstract: CAMBRIA-1 and CAMBRIA-2 are ongoing, randomized, open-label trials of adjuvant camizestrant, either as an upfront treatment or as a treatment after standard endocrine therapy, in patients with HR+/HER2- early breast cancer at intermediate to high risk..."

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Women's Health • ER • HER-2

Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. (ASCO 2025) - P3 | " Pts with HR+/HER2– ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib) were enrolled and had ctDNA tested for ESR1m every 2–3 months, coinciding with routine imaging. Camizestrant + CDK4/6i guided by emergence of ESR1m during 1L AI + CDK4/6i in pts with HR+/HER2– ABC resulted in a statistically significant and clinically meaningful improvement in PFS. SERENA-6 is the first global Phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression. These findings represent a potential new treatment strategy to optimize and improve 1L patient outcomes."

Circulating tumor DNA • Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2- advanced breast cancer: Results from SERENA-1. (PubMed, Clin Cancer Res) - P1 | "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."

Journal • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. (PubMed, N Engl J Med) - P3 | "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.)."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (SABCS 2025) - "Methods SERENA-6, a randomized, double-blind, phase 3 trial, enrolled pts with HR+/HER2- ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (palbociclib/ribociclib/abemaciclib). No new safety signals were observed. These results further support an early switch to CAMI + CDK4/6i during 1L therapy to delay disease progression."

Circulating tumor DNA • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

The SERENA-4 Phase III trial of AstraZeneca’s Etcamah (camizestrant) in combination with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, did not meet the primary endpoint of progression-free survival (PFS) (AstraZeneca Press Release) - "...However a numerical improvement was observed in the upfront 1st-line treatment of patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer who have not received any systemic treatment for advanced disease....The safety profile of Etcamah in combination with palbociclib in SERENA-4 was consistent with the known safety profile of each medicine, with no new safety concerns identified. Data will be shared in due course."

P3 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Pharmacodynamics of Camizestrant Treatment in Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer: Results From the Randomized, Presurgical SERENA-3 Study. (PubMed, J Clin Oncol) - "SERENA-3 demonstrates that camizestrant 75 mg once daily (Phase III dose) is well-tolerated and achieves maximal reduction in ER through known mechanisms, that is, antagonism and degradation, by 5-7 days, and proliferation suppression determined by Ki67 expression, by 12-15 days. These data support camizestrant 75 mg once daily as the preferred dose for ongoing clinical development and highlight the importance of presurgical WOO studies in guiding dose selection."

Journal • PK/PD data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Onco360…has been selected as a national pharmacy partner by AstraZeneca for Etcamah (camizestrant), which is indicated for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer upon detection of ESR1 mutation during aromatase inhibitor (AI) and CDK4/6 inhibitor therapy… (GlobeNewswire)

Commercial • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

First-line (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer (ABC): Final progression-free survival 2 (PFS2) from the phase III SERENA-6 trial. (ASCO 2026) - P3 | "Switching to CAMI + CDK4/6i at ESR1m emergence continued to result in PFS benefit, with approximately a third of pts still progression-free at 30 mo. PFS benefit was maintained beyond first progression; PFS2 was significantly improved and the clinically meaningful endpoint of chemotherapy/ADC-free survival was prolonged vs continuing AI + CDK4/6i. These results continue to support a switch to CAMI + CDK4/6i for pts with ESR1m during 1L therapy to delay disease progression and deteriorations in QoL."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • PIK3CA • TP53

Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose Phase 2 SERENA-2 trial (SABCS 2022) - No abstract available

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. (PubMed, Future Oncol) - P3 | "Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety."

Clinical • Journal • P3 data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

SERENA-3: A randomized pre-surgical window of opportunity study assessing dose and duration of camizestrant treatment in post-menopausal women with ER-positive, HER2-negative primary breast cancer (SABCS 2023) - P2 | "Background Camizestrant, a next-generation oral selective estrogen receptor (ER) degrader (SERD) and pure ER antagonist, has demonstrated statistically significant and clinically meaningful progression-free survival (PFS) benefit over fulvestrant at both 75 and 150 mg once-daily doses in the Phase 2 SERENA-2 (NCT04214288) study in post-menopausal women with ER+ HER2- advanced breast cancer. Together with SERENA-2, this provides strong evidence supporting 75 mg as the optimal dose of camizestrant, including for the early disease setting, and highlights the additive value of a specifically designed multi-dose pre-surgical PD study for optimal dose selection. Table 1"

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A Phase 1 dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results. (PubMed, Ann Oncol) - P1, P2 | "Camizestrant is a next-generation oral SERD and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75, 150 and 300 mg QD doses for Phase 2 testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298)."

Journal • Metastases • Monotherapy • P1 data • Breast Cancer • Cardiovascular • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Dynamics of ESR1 mutation (ESR1m) circulating tumour DNA (ctDNA) in patients (pts) with estrogen receptor (ER)+ HER2- metastatic breast cancer (mBC) receiving camizestrant or fulvestrant: Exploratory analyses from the SERENA-2 trial (ESMO-BC 2024) - P2, P3 | "The relationship between C2D1 suppression and median PFS suggests early changes in ctDNA may predict for better response to camizestrant treatment. The efficacy of camizestrant in pts with detectable ESR1m is being prospectively tested in the SERENA-6 trial (NCT04964934)."

Circulating tumor DNA • Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer."

Clinical • Journal • Metastases • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Switching ahead of progression: Insights from the SERENA-6 trial on targeting emerging ESR1 mutations in advanced HR+/HER2- breast cancer. (PubMed, Med) - "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."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC) (ESMO 2025) - P3 | "NR, not reached. Conclusions Together with the clinical efficacy and manageable safety profile of CAMI + CDK4/6i, the PROs from the SERENA-6 trial support this combination as a potential new treatment strategy to optimise and improve outcomes in patients with HR+/HER2– ABC and emergence of ESR1 m, ahead of disease progression, during 1L AI + CDK4/6i."

Clinical • Metastases • Patient reported outcomes • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Emergence of ESR1 mutations (ESR1m) in ctDNA during first-line (1L) endocrine-based therapy in HR+/HER2_ advanced breast cancer: Findings from the SERENA-6 trial (ESMO-BC 2026) - P3 | "Background: In SERENA-6, switching to camizestrant, with continuation of CDK4/6i, guided by ESR1m emergence during 1L therapy with AI+CDK4/6i and ahead of disease progression, significantly improved PFS vs continuing AI+CDK4/6i... While ESR1m were more frequently identified with the first test in SERENA-6, continuing to test identified many more pts with an ESR1m, supporting ongoing testing. Data from SERENA-6 show that all pts should be tested for ESR1m, regardless of how long they have been on AI+CDK4/6i; testing should continue alongside routine clinical evaluations in those with an initial negative result until ESR1m emergence or disease progression."

Circulating tumor DNA • Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

FDA grants accelerated approval to camizestrant with a CDK4/6 inhibitor for ESR1-Mutated HR-positive, HER2-negative locally advanced or metastatic breast cancer (FDA) - "FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer with ESR1 mutations for treatment with camizestrant...Efficacy was evaluated in SERENA-6 (NCT04964934), a randomized, double-blind, placebo-controlled, multicenter trial to assess switching to camizestrant in combination with a CDK4/6 inhibitor versus continuing an aromatase inhibitor (AI) in combination with a CDK4/6 inhibitor in adult patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer with detectable ESR1 mutations....The recommended camizestrant dose is 75 mg orally once daily, with or without food, until disease progression or unacceptable toxicity."

Accelerated approval • Companion diagnostic • FDA approval • Project Orbis • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Oral selective estrogen receptor degraders and biomarker-driven therapy in ER-positive breast cancer: mechanisms, clinical evidence, and future directions. (PubMed, Front Oncol) - "This review comprehensively examines the mechanisms of SERD action, their role in overcoming resistance to conventional endocrine therapy, and clinical applications of approved agents including fulvestrant, elacestrant, imlunestrant, and vepdegestrant, the first FDA-approved PROTAC estrogen receptor degrader. We discuss emerging oral SERDs such as giredestrant and camizestrant, novel PROTAC-based approaches, and combination strategies with CDK4/6 inhibitors, PI3K inhibitors, and other targeted agents. Special attention is given to ESR1 mutations as biomarkers for patient selection and therapy optimization. The review highlights key clinical trials including EMERALD, EMBER-3, SERENA-6, and lidERA that have shaped current treatment guidelines and points toward future directions in SERD development."

Biomarker • Journal • Review • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Gynecology • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ER

An Adjuvant Endocrine-based Therapy Study of Camizestrant (AZD9833) in ER+/HER2- Early Breast Cancer (CAMBRIA-2) (clinicaltrials.gov) - P3 | N=5511 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ER • HER-2