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

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

Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 Phase III trial (Businesswire) - P3 | N=315 | SERENA-6 (NCT04964934) | Sponsor: AstraZeneca | "Positive high-level results from a planned interim analysis of the SERENA-6 Phase III trial showed that AstraZeneca’s camizestrant in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) demonstrated a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS)....The key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the time of this interim analysis. However, the camizestrant combination demonstrated a trend toward improvement in PFS2. The trial will continue as planned to further assess key secondary endpoints."

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

New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor-Positive Breast Cancer. (PubMed, Annu Rev Med) - "There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs."

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

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=204 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2025 ➔ May 2026 | Trial primary completion date: Jun 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor 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=396 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Sep 2024 ➔ Jul 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 randomized phase III study of first-line saruparib (AZD5305) + camizestrant vs CDK4/6i plus physician's choice endocrine therapy or + camizestrant in patients w/ BRCA1/BRCA2/PALB2 mutations & HR+/HER2- advanced breast cancer (EvoPAR-Breast01) (SABCS 2024) - 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. Participant enrollment is ongoing. Approximately 500 participants will be randomized across the three arms."

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 • BRCA1 • BRCA2 • CDK4 • HER-2 • HRD • PALB2 • PGR

Results from SERENA-1 Parts K/L: A Phase 1 study of the next-generation oral selective estrogen receptor degrader (SERD) camizestrant (AZD9833) in combination with ribociclib in women with ER-positive, HER2 negative advanced breast cancer. (SABCS 2024) - P1, P3 | "Study parts examining camizestrant as monotherapy and in combination with palbociclib, abemaciclib, and capivasertib have been presented previously...Overall, patients were heavily pre-treated in the advanced setting; 17/58 (29%) patients had received prior chemotherapy, 40/58 (69%) prior CDK4/6i, and 28/58 (48%) prior fulvestrant...Conclusion Camizestrant 75 mg in combination with ribociclib 400 or 600 mg was well tolerated, consistent with data for each drug individually, and resulted in ESR1m ctDNA suppression in 85% of patients with ESR1m at baseline. This combination is included in the ongoing Phase 3 SERENA-6 trial (NCT04964934) of camizestrant combined with CDK4/6i versus an aromatase inhibitor plus CDK4/6i in patients with detectable ESR1m during first-line therapy, which will further clarify the role of camizestrant in the treatment of patients with ER+/HER2− advanced breast cancer."

Clinical • Combination therapy • Metastases • P1 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

The addition of ribociclib, palbociclib or abemaciclib to the next generation oral SERD, camizestrant, delivers greater anti-tumour efficacy in a range of ESR1wt and ESR1m breast PDX models (SABCS 2024) - P3 | "Camizestrant is a next generation oral selective estrogen receptor degrader (ngSERD) and pure ER antagonist that has demonstrated superior activity to fulvestrant both pre-clinically and clinically. These preclinical data demonstrate consistent activity of camizestrant in combination with all three globally approved CDK4/6i. This, together with the efficacy of camizestrant in patients with ESR1wt and ESR1m tumours, suggests camizestrant in combination with CDK4/6i has the potential to provide extended benefit for patients with ER+/HER2 metastatic breast cancer in the first line setting, a concept under clinical investigation in the ongoing SERENA-6 (NCT04964934) and SERENA-4 (NCT04711252) studies."

Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • CCND1 • ER • HER-2

Selective activity of rogaratinib in PIK3CA- and ESR1-wild-type, FGFR1/2-amplified hormone receptor-positive breast cancer (HR+/HER2- BC): a co-clinical trial (SABCS 2024) - "PDTOs viability was explored in response to rogaratinib, fulvestrant, palbociclib, camizestrant, and alpelisib in monotherapy or in combinations. A high percentage (43%) of second-line HR+/HER2- BC displays FGFR1/2 overexpression or amplification, of which approximately half are wild-type for ESR1 and PIK3CA. FGFR1/2 inhibition with rogaratinib in combination with palbociclib and fulvestrant is active in second-line, FGFR1/2-amplified/overexpressed HR+/HER2- BC, but the activity is restricted to wild-type PIK3CA/ESR1 patients. These results frame the population in which the development of this combination should be focused."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • FGFR1 • HER-2 • PIK3CA