camizestrant (AZD9833) / AstraZeneca - LARVOL DELTA

Safety profile of post-CDK4/6 treatments in HR+/HER2− metastatic breast cancer (mBC): A network meta-analysis (AACR 2026) - "Among ET-based strategies, the lowest RRs were observed for: imlunestrant alone (0.98, 95% CI 0.92-1.05) for any G AEs; camizestrant 75 mg (0.81, 0.36-1.83) for G≥3 AEs; elacestrant (1.45, 0.66-3.16) for AEs leading to discontinuation. While among antibody-drug conjugates (ADCs) the lowest RRs were observed for: sacituzumab govitecan (SG) for any G AEs (1.00, 0.99-1.01); datopotamab deruxtecan (Dato-DXd) (0.47, 0.37-0.59) for G≥3 AEs; SG (0.83, 0.26-2.66) for AEs leading to discontinuation...Among ET-based options, novel mono-ETs (oral SERDs and PROTACs) showed the lowest risk of discontinuation and G≥3 AEs. Among ADCs, TROP2-directed agents had fewer discontinuations, while ADCs with DXd as a payload showed higher rates of any G AEs but (except for DESTINY-Breast06) lower G≥3 AEs risk than other tx strategies."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Monitoring response to camizestrant next-generation oral SERD in ER+ advanced breast cancer patient-derived xenografts via circulating tumor DNA profiling (AACR 2026) - "This study establishes a robust, minimally invasive preclinical platform for evaluating ctDNA-based biomarkers and treatment efficacy in oncology research. The approach enables investigation of ctDNA release biology and treatment response in preclinical models that are difficult to address using human samples alone. These findings demonstrate the translational potential of preclinical ctDNA monitoring to inform clinical biomarker strategies and optimize therapeutic development in ER+ breast cancer."

Circulating tumor DNA • Clinical • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

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

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

Identification, synthesis, and characterization of a unique N-glucuronide of an acid metabolite of camizestrant (AZD9833) in humans. (PubMed, Drug Metab Dispos) - "SIGNIFICANCE STATEMENT: Metabolite M14 of camizestrant (AZD9833), a major circulating metabolite in humans, was successfully identified as an N-glucuronide of an acid metabolite of camizestrant, and its unusual chromatographic and stability properties were characterized. The development of a novel hybrid chemical and biological synthesis for M14 has introduced a new approach to synthesizing glucuronides of compounds with acidic functional groups that otherwise interfere with their own in vitro glucuronidation."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

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

MEDOPP0555: PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CAMIZESTRANT PLUS RIBOCICLIB IN PATIENTS WITH HORMONE RECEPTOR-POSITIVE (HR+) BREAST CANCER? (THE CADILLAC STUDY) (clinicaltrialsregister.eu) - P1/2 | N=131 | Recruiting | Sponsor: Medica Scientia Innovation Research S.L., Medica Scientia Innovation Research S.L. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • Hormone Receptor 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

Updated Results and an Exploratory Analysis of ESR1 Mutations (ESR1m) Circulating Tumor DNA (ctDNA) Dynamics From SERENA-6, a Phase III Trial of Camizestrant + CDK4/6 Inhibitor (CDK4/6i) for Emergent ESR1m During First-Line (1L) Endocrine-Based Therapy and Ahead of Disease Progression in Patients With HR+/HER2– Advanced Breast Cancer (ABC) (MBCC 2026) - No abstract available

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

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=396 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2025 ➔ Dec 2026

First-in-human • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=305 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Dec 2022 ➔ Oct 2023

First-in-human • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=276 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2023 ➔ Sep 2023 | Trial primary completion date: May 2022 ➔ Oct 2022

First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • 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. (DKK 2026) - P3 | " Pts with HR+/HER2– ABC, ≥6 months on 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib), had ctDNA testing for ESR1m every 2–3 months, coinciding with imaging. Camizestrant + CDK4/6i, guided by ESR1m emergence on 1L AI + CDK4/6i in HR+/HER2– ABC, yielded significant and clinically meaningful PFS improvement. SERENA-6 is the first global Phase 3 trial showing clinical utility of ctDNA-guided resistance detection and intervention before progression. Clinical trial: NCT04964934."

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

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=168 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Nov 2021 ➔ Oct 2020

First-in-human • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=168 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2022 ➔ Mar 2023

First-in-human • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=240 | Not yet recruiting | Sponsor: AstraZeneca

First-in-human • New P1 trial • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • ER • HER-2

CYCAD-1: A First-in-human Dose Escalation and Expansion Study to Evaluate the Safety, and Tolerability of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=564 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2026 ➔ Aug 2027

First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=340 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Sep 2023 ➔ Dec 2023

First-in-human • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=270 | Recruiting | Sponsor: AstraZeneca | N=168 ➔ 270

Enrollment change • First-in-human • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=168 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Nov 2021 ➔ Apr 2022 | Trial primary completion date: Oct 2020 ➔ Mar 2021

First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=396 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2025 ➔ Nov 2025

First-in-human • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=402 | Recruiting | Sponsor: AstraZeneca | N=305 ➔ 402 | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=182 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Mar 2021 ➔ Jan 2022

First-in-human • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=403 | Recruiting | Sponsor: AstraZeneca | Trial completion date: May 2024 ➔ Sep 2024 | Trial primary completion date: May 2024 ➔ Aug 2024

First-in-human • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2