camizestrant (AZD9833) / AstraZeneca - LARVOL DELTA

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

Camizestrant/Ribociclib Improves PFS and Responses in ER+/HER2– Breast Cancer (Cancer Network) - P1 | N=396 | SERENA-1 (NCT03616587) | Sponsor: AstraZeneca | "Results from the multicenter, first-in-human phase 1 SERENA-1 trial (NCT03616587) presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) showed that camizestrant plus ribociclib (Kisqali) demonstrated clinically meaningful efficacy and tolerability outcomes in patients with estrogen receptor (ER)–positive, HER2– advanced breast cancer....The median progression-free survival (PFS) was 8.1 months (95% CI, 1.9-NE) in the 400 mg arm and 8.1 (95% CI, 2.0-NE) months in the 600 mg arm, while the objective response rate (ORR) with measurable or non-measurable disease at baseline was 11.1% (3/27) in the 400 mg arm and 12.5% (4/32) in the 600 mg arm....CBR24 rates were 55.6% and 47.6% among patients who had received prior fulvestrant (Faslodex), 56.0% and 53.1% among patients who had received a prior CDK4/6 inhibitor (CDK4/6i), and 56.3% and 66.7% among patients in whom an ESR1 mutation was detected."

P1 data • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Key Factors Affecting Clinical Investigators Use of Oral SERDs in Current Management of ER-Positive, HER2-Negative, ESR1-Mutated (ER+/HER2-/ESR1+) Metastatic Breast Cancer That Has Relapsed After Treatment w/ a CDK4/6 Inhibitor/Endocrine Therapy (SABCS 2024) - "Background: The January 2023 FDA approval of the novel SERD elacestrant (E) provided an important new therapeutic consideration for patients with relapsed ER+/HER2-/ESR1+ metastatic BC... For a 65-year-old woman with ER+/HER2-/ESR1+ BC who experiences a recurrence of minimally symptomatic bone metastases 18 months after treatment with CDKi/fulvestrant (ful), 19 of 20 CIs would recommend E. When the duration of benefit from the CDKi/ful was reduced to 12 months, 17 of 20 CIs continued to favor the SERD...Similarly, for a 65-year-old woman with ER+/HER2-/ESR1+ BC who also has a PIK3CA mutation and experiences a recurrence of minimally symptomatic bone metastases 18 months after treatment with a CDKi/ful, CIs were largely split between E (10) and capivasertib (capi)/ET (7)...In terms of perspectives on the investigational SERDs imlunestrant and camizestrant, at the current time, CIs largely view their efficacy and tolerability to be similar to that of E or they are unable..."

Clinical • 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

MODULE 5: Oral Selective Estrogen Receptor Degraders (SERDs) for HR-Positive mBC (SABCS 2024) - "This CME symposium is sponsored by Research To Practice, and supported by educational grants from AstraZeneca Pharmaceuticals LP, Eli Lilly, Novartis, and Stemline Therapeutics Inc. Incidence of ESR1 mutations in endocrine-resistant breast cancer; optimal timing and approach to testing Results from the Phase III EMERALD trial evaluating elacestrant versus standard endocrine monotherapy for pretreated HR-positive, HER2-negative mBC; outcomes for patients with and without ESR1 mutations FDA approval of elacestrant for previously treated HR-positive, HER2-negative mBC with ESR1 mutations; optimal incorporation into clinical management algorithms Available findings with other oral SERDs (eg, camizestrant, imlunestrant, giredestrant) alone and in combination with other systemic therapies for HR-positive, HER2-negative mBC Comparative side-effect profiles of approved and investigational oral SERDs; optimal monitoring for and management of AEs Ongoing efforts evaluating oral..."

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

Congratulations @ErikaHamilton9 and Team: Camizestrant,a next-gen oral SERD, v fulvestrant in post-menopausal women with ER+, HER2- ABC (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial - Lancet Oncology @SarahCannonDocs @SCRIOncology

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

EvoPAR-BR01: Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2030 ➔ Oct 2030

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (clinicaltrials.gov) - P3 | N=312 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Circulating tumor DNA • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review. (PubMed, Cancer Treat Rev) - "Oral SERDs constitute an exciting new drug class. Ongoing and future research will further refine the role of these drugs next to standard endocrine treatments and targeted therapies."

Journal • Review • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER

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 | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open

A multiomic approach for camizestrant-induced estrogen receptor (ER) degradation, antagonism and anti-proliferation: Exploratory analysis from SERENA-3 (ESMO 2024) - P2 | "Complementary multiomic assessment of SERENA-3 showed that camizestrant 75 mg achieved maximal levels of ER degradation and antagonism at 5-7 days, and proliferation suppression by 12–15 days, affirming the conclusion from IHC analysis and its selection as the primary endpoint, allowing comparison with prior pre-surgical studies. These results highlight the different temporal nature of the PD effects and suggest the utility of the endpoints as primary readouts for PD assessment in future trials. Together with SERENA-2, this evidence supports 75 mg as the optimal camizestrant dose, including in early disease, and highlights the value of a specific multi-dose pre-surgical pharmacodynamic study for dose selection."

Breast Cancer • Oncology • Solid Tumor • ER

EvoPAR-BR01: Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2024 ➔ Aug 2024

Enrollment open • Metastases • Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

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 | Not yet recruiting | Sponsor: AstraZeneca

Combination therapy • New P1 trial