camizestrant (AZD9833) / AstraZeneca - LARVOL DELTA

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

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

Saruparib + camizestrant: Data from P3 EvoPAR-Breast01 trial (NCT06380751) for HR+/HER2-negative advanced breast cancer post 2027 (AstraZeneca) - FY 2025 Results

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

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) - 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

Camizestrant: Data from P3 SERENA-4 trial (NCT04711252) for HR+/HER2-negative advanced breast cancer in H2 2026 (AstraZeneca) - FY 2025 Results

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Camizestrant: Data from P3 CAMBRIA-1 trial (NCT05774951) for ER+/HER2-negative early breast cancer 2027 (AstraZeneca) - FY 2025 Results: Data from P3 CAMBRIA-2 trial (NCT05952557) for ER+/HER2-negative early breast cancer post 2027

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

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

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

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

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: Dec 2026 ➔ Jun 2027

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

Camizestrant in combination with capivasertib for women with ER-positive, HER2-negative advanced breast cancer: results from SERENA-1. (PubMed, ESMO Open) - P1 | "In these pretreated participants, camizestrant 75 mg in combination with capivasertib 400 mg was well tolerated, with a side effect profile consistent with each drug as monotherapy, and showed encouraging evidence of clinical efficacy."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN

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

Open-Label Study Assessing Relative and Absolute Bioavailability of Oral Camizestrant Formulations and Food Effects in Healthy Postmenopausal Women. (PubMed, Clin Transl Sci) - "The formulations showed similar exposures, supporting the planned manufacturing changes. Camizestrant exhibited moderate bioavailability; exposures were similar under fasted and high-fat meal conditions, supporting its administration with or without food."

Clinical • Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

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, 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

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 | N=348 ➔ 564

Enrollment change • First-in-human • 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

Selective Estrogen Receptor Degraders Induce Bradycardia by Modulating Nuclear Estrogen Signaling. (PubMed, JACC Basic Transl Sci) - "Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart rate. Mutations in gper, esr2a, and esr2b did not confer resistance to SERD-induced bradycardia, whereas esr1 mutant embryos were protected. These findings demonstrate that SERD-associated bradycardia is mediated through Esr1 signaling, supporting an on-target adverse effect."

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

MODULE 3: Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) (SABCS 2025) - "Sponsored by Genentech, a member of the Roche Group, Eli Lilly and Stemline Therapeutics Inc. Optimal approach to and timing of the assessment of relevant biomarkers for patients with HR-positive mBC; increasing relevance of biomarker evaluation in the up-front setting Long-term follow-up from pivotal clinical trials and other relevant research efforts, such as the RIGHT Choice and ABIGAIL trials, evaluating CDK4/6 inhibitors for HR-positive, HER2-negative mBC; factors affecting the selection of a CDK4/6 inhibitor and an endocrine partner Key findings from the Phase III INAVO120 study evaluating inavolisib in combination with palbociclib and fulvestrant as first-line therapy for patients with HR-positive, HER2-negative mBC with a PIK3CA mutation whose disease had progressed during or within 12 months of adjuvant endocrine therapy FDA approval of inavolisib/palbociclib/fulvestrant and clinical role in the treatment of newly diagnosed HR-positive, HER2-negative mBC with a..."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA