camizestrant (AZD9833) / AstraZeneca - LARVOL DELTA

Visual symptom questionnaire results from SERENA-6, a Phase 3 study of switch to camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) at emergence of ESR1m during first-line (1L) therapy for patients (pts) with HR+/HER2– advanced breast cancer (ABC) (ESMO 2025) - No abstract available

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • 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) - No abstract available

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

Camizestrant: Data from P3 SERENA-6 trial (NCT04964934) for ESR1m HR+/HER2-negative advanced breast cancer in H1 2026 (AstraZeneca) - H1 and Q2 2025 Results: Data from P3 SERENA-4 trial (NCT04711252) for HR+/HER2-negative advanced breast cancer in H2 2026

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 post 2026 (AstraZeneca) - H1 and Q2 2025 Results: Data from P3 CAMBRIA-2 trial (NCT05952557) for ER+/HER2-negative early breast cancer post 2026

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

Saruparib + camizestrant: Data from P3 EvoPAR-Breast01 trial (NCT06380751) for HR+/HER2-negative advanced breast cancer post 2026 (AstraZeneca) - H1 and Q2 2025 Results

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

The application of mechanistic absorption, distribution, metabolism and excretion studies and physiologically-based pharmacokinetic modeling in the discovery of the next-generation oral selective estrogen receptor degrader camizestrant to achieve an acceptable human pharmacokinetic profile. (PubMed, Drug Metab Dispos) - "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."

Journal • PK/PD data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CYP3A4 • 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. (BASCO-MN 2025) - No abstract available

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 • ER • HER-2

PETRA: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=804 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2027 ➔ Jun 2027 | Trial primary completion date: Mar 2027 ➔ Jun 2027

Monotherapy • Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

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: “Camizestrant + CDK4/6i reduced the risk of progression or death by 56%”; Breast cancer (AstraZeneca) - ASCO 2025: “Camizestrant + CDK4/6i is well-tolerated with a very low discontinuation rate (<1.5%)”

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

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

Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (clinicaltrials.gov) - P3 | N=315 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Apr 2025 ➔ Jul 2025

Circulating tumor DNA • 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 reduced the risk of disease progression or death by 56% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 Phase III trial (AstraZeneca Press Release) - P3 | N=315 | SERENA-6 (NCT04964934) | Sponsor: AstraZeneca | "Results showed the camizestrant combination reduced the risk of disease progression or death by 56% compared to standard-of-care treatment (based on a hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.31–0.60; p<0.00001) as assessed by investigator. Median PFS was 16.0 months for patients who switched to the camizestrant combination versus 9.2 months for the comparator arm. Importantly, a consistent PFS benefit was observed across all CDK4/6 inhibitors and clinically relevant subgroups in the trial, including analysis by age, race, region, time of ESR1 mutation detection and type of ESR1 mutation....Data for the key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis."

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

Ongoing and Proposal Trials (BCT) (GBCC 2025) - "The current recruiting BCT portfolio includes: EXPERT, using PAM50 to guide omission of radiotherapy after breast conserving surgery; OPTIMA, investigating PAM50-directed systemic therapy for node positive ER+ breast cancer; Neo-N, investigating a 12-week neoadjuvant course of carboplatin, paclitaxel, relatlimab and nivolumab for stage I and II TNBC; TUGETHER, investigating trastuzumab, tucatinib and pembrolizumab for pre-treated metastatic HER2+ breast cancer; OLIO, investigating neoadjuvant paclitaxel, Olaparib and durvalumab for young women with HRD-positive, ER+ early breast cancer; and CAMBRIA-2, an international phase 3 trial of adjuvant camizestrant for high risk ER+ breast cancer. BCT has working specialty subgroups and a scientific committee; a concept development workshop annually; an annual Scientific Meeting; and initiatives to support young investigators and proof-of- principle projects in addition to major project coordination. BCT recognises the..."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • HRD

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=348 | Recruiting | Sponsor: AstraZeneca | N=204 ➔ 348

Enrollment change • Breast Cancer • HER2 Breast Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor

AstraZeneca’s record seventh year of plenary data at ASCO furthers ambition to redefine breast cancer care and transform outcomes in gastric cancer (AstraZeneca Press Release) - "AstraZeneca advances its ambition to eliminate cancer as a cause of death with new data across its diverse, industry-leading portfolio and pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, 30 May to 3 June 2025. More than 80 abstracts will feature 20 approved and potential new medicines from the Company including two plenary presentations, one special late-breaking oral abstract session and 19 additional oral presentations."

Clinical data • Bladder Cancer • Cervical Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy. (PubMed, Breast Cancer Res) - "Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. Co-mutations in actionable pathways, particularly PIK3CA, were observed in n = 10 ESR1 mutant tumors (41.6%), highlighting their contribution to resistance mechanisms and posing significant challenges for treatment selection, as these alterations may necessitate combination therapies to effectively target multiple resistance pathways. This study presents new insights into the prevalence and clinical significance of ESR1 mutations in HR + /HER2- MBC, highlighting the potential utility of FFPE biopsy samples as a viable alternative or complementary approach to LB for mutation detection, particularly in resource-limited settings where access to ctDNA analysis may be constrained."

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 • CCDC170 • ER • HER-2 • PIK3CA

Camizestrant: Data from P3 CAMBRIA-1 trial (NCT05774951) for ER+/HER2-negative early breast cancer after at least 2 years of standard adjuvant endocrine therapy post 2026 (AstraZeneca) - Q1 2025 Results: Data from P3 CAMBRIA-2 trial (NCT05952557) for ER+/HER2-negative early breast cancer post 2026

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

Camizestrant: Data from P3 SERENA-4 trial (NCT04711252) for HR+/HER2-ve advanced breast cancer in 2026 (AstraZeneca) - Q1 2025 Results

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

ET-Based Combinations and Novel Agents in HR+/HER2- Advanced Breast Cancer (GBCC 2025) - "Tumors with alterations in the PIK3CA/AKT/PTEN pathway may be offered a pathway inhibitor such as capivasertib or alpelisib, and patients with high risk recurrence of HR+ disease with a PIK3CA mutation may benefit from early introduction of a first-line inavolisib triplet...The oral SERD elacestrant is approved as monotherapy in pretreated patients with tumors harboring an ESR1 mutation. Additional oral SERDs, including imlunestrant, camizestrant, and giredestrant, have demonstrated activity and are in registrational trials. An additional maneuver in the pretreated space includes continuation of a CDK4/6 inhibitor after prior CDK4/6 inhibitor, with activity seen from switching to abemaciclib or ribociclib from a prior agent, and novel CDK inhibitors are in trials as a next generation approach. The mTOR inhibitor everolimus remains an option for pretreated patients as well, particularly when actionable mutations are not present. The continued introduction of novel agents..."

Metastases • 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 • PIK3CA

SERENA-2: A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer (clinicaltrials.gov) - P2 | N=240 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Apr 2026

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

A Randomized Phase 3 Study of First-Line Saruparib (AZD5305) Plus Camizestrant Versus CDK4/6i Plus Physician's Choice Endocrine Therapy or CDK4/6i Plus Camizestrant in Patients With HR+/ HER2– Advanced Breast Cancer With BRCA1/BRCA2/PALB2 Mutations (EvoPAR-B) (MBCC 2025) - P3 | "Participants will be randomized 2:2:1 to receive saruparib plus camizestrant, physician's choice CDK4/6i (abemaciclib, ribociclib, or palbociclib) plus physician's choice ET (fulvestrant, letrozole, anastrozole, or exemestane), or physician's choice CDK4/6i plus camizestrant, respectively. Status Participant enrollment is ongoing across 185 trial locations in 20 countries. Approximately 500 participants will be randomized across the 3 arms."

Clinical • Metastases • 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 • BRCA1 • BRCA2 • CDK4 • HER-2 • HRD • PALB2

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

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

A Study to Investigate the Pharmacokinetics of Midazolam After Repeated Doses of Camizestrant (AZD9833) and to Investigate the Pharmacokinetics of Camizestrant When Administered Alone and in Combination With Carbamazepine in Healthy Post-Menopausal Female Participants (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2025 ➔ Jul 2025 | Trial primary completion date: Feb 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date

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