Saruparib + Camizestrant for Breast Cancer

(EvoPAR-BR01 Trial)

Recruiting in Palo Alto (17 mi)

+223 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers, CYP2B6 substrates

Disqualifiers: MDS/AML, Severe cytopenia, Hepatitis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients with BRCA1, BRCA2, or PALB2m, HR-positive, HER2-negative (defined as IHC 0, 1+, 2+/ ISH non-amplified) advanced breast cancer.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must avoid using specific drugs, including strong and moderate CYP3A4 inducers/inhibitors, sensitive CYP2B6 substrates, and certain CYP2C9 and CYP2C19 substrates, at least 21 days before starting the trial. Check with the trial team to see if your current medications are on this list.

What data supports the effectiveness of the drug camizestrant for breast cancer?

Research shows that camizestrant, an oral drug that targets estrogen receptors, significantly improved the time patients lived without their cancer getting worse compared to another drug, fulvestrant, in women with advanced breast cancer. It also worked well in patients who had previously received other treatments and in those with specific genetic mutations.

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Eligibility Criteria

This trial is for adults with advanced breast cancer that's HR-positive, HER2-negative, and has specific mutations (BRCA1, BRCA2, or PALB2). Participants should have good organ function and an ECOG performance status of 0 or 1. They must not have had certain treatments recently and should be able to swallow pills. People with severe nausea, GI diseases, bleeding disorders, active infections like HIV or hepatitis B/C, heart issues, or those on conflicting medications can't join.

Inclusion Criteria

My organs and bone marrow are working well.

My breast cancer cannot be cured with surgery or has spread to other parts.

My breast cancer is HR-positive and HER2-negative.

Exclusion Criteria

I have severe, ongoing nausea or a chronic stomach condition that makes it hard for me to swallow pills.

I have had recent palliative radiotherapy.

I have not received blood products or growth factors in the last 28 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive saruparib (AZD5305) plus camizestrant or physician's choice CDK4/6 inhibitor plus endocrine therapy or camizestrant until disease progression or unacceptable toxicity

Up to approximately 59 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 88 months

Participant Groups

The study tests the effectiveness of Saruparib (AZD5305) combined with Camizestrant against standard CDK4/6 inhibitors plus endocrine therapy in treating advanced breast cancer. It aims to see if this new combination works better for patients who haven't responded well to other treatments.

Group I: Arm 3: Physician's choice CDK4/6i plus camizestrant Experimental Treatment 4 Interventions

participants will receive camizestrant orally. Agents for CDK4/6i treatment are indicated above and should follow local guidelines

Group II: Arm 1: saruparib (AZD5305) plus camizestrant Experimental Treatment 2 Interventions

participants will receive saruparib (AZD5305) orally and camizestrant orally

Group III: Arm 2: Physician's choice CDK4/6i plus physician's choice ET Active Control 7 Interventions

agents are indicated below and should follow local guidelines: * Physician's Choice CDK4/6i: * abemaciclib orally, or * ribociclib orally, or * palbociclib orally. * Physician's Choice ET: * fulvestrant intramuscularly, or * One of the following AIs: * letrozole orally, or * anastrozole orally, or * exemestane orally

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Aurora, CO

Research Site Boston, MA

Research Site Dearborn, MI

Research Site Silver Spring, MD

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Second Oral SERD Shines in ER+ Breast Cancer. [2023] The first data from the phase II SERENA-2 trial look promising for the investigational oral selective estrogen receptor degrader camizestrant. Compared with standard fulvestrant, it significantly prolonged progression-free survival in postmenopausal women with advanced estrogen receptor-positive, HER2-negative breast cancer. Camizestrant also bested fulvestrant in subgroup analyses of patients who previously received a CDK4/6 inhibitor, had visceral metastases, or had ESR1 mutations.

2. United States pubmed.ncbi.nlm.nih.gov

The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance. [2023] Oral selective estrogen receptor degraders (SERD) could become the backbone of endocrine therapy (ET) for estrogen receptor-positive (ER+) breast cancer, as they achieve greater inhibition of ER-driven cancers than current ETs and overcome key resistance mechanisms. In this study, we evaluated the preclinical pharmacology and efficacy of the next-generation oral SERD camizestrant (AZD9833) and assessed ER-co-targeting strategies by combining camizestrant with CDK4/6 inhibitors (CDK4/6i) and PI3K/AKT/mTOR-targeted therapy in models of progression on CDK4/6i and/or ET. Camizestrant demonstrated robust and selective ER degradation, modulated ER-regulated gene expression, and induced complete ER antagonism and significant antiproliferation activity in ESR1 wild-type (ESR1wt) and mutant (ESR1m) breast cancer cell lines and patient-derived xenograft (PDX) models. Camizestrant also delivered strong antitumor activity in fulvestrant-resistant ESR1wt and ESR1m PDX models. Evaluation of camizestrant in combination with CDK4/6i (palbociclib or abemaciclib) in CDK4/6-naive and -resistant models, as well as in combination with PI3Kαi (alpelisib), mTORi (everolimus), or AKTi (capivasertib), indicated that camizestrant was active with CDK4/6i or PI3K/AKT/mTORi and that antitumor activity was further increased by the triple combination. The response was observed independently of PI3K pathway mutation status. Overall, camizestrant shows strong and broad antitumor activity in ER+ breast cancer as a monotherapy and when combined with CDK4/6i and PI3K/AKT/mTORi.

3. England pubmed.ncbi.nlm.nih.gov

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. [2023] ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). 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. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/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.

4. United States pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. [2021] Label="PURPOSE">Fulvestrant, the first-in-class selective estrogen receptor (ER) degrader (SERD), is clinically effective in patients with ER+ breast cancer, but it has administration and pharmacokinetic limitations. Pharmacodynamic data suggest complete ER degradation is not achieved at fulvestrant's clinically feasible dose. This presurgical study (NCT03236974) compared the pharmacodynamic effects of fulvestrant with AZD9496, a novel, orally bioavailable, nonsteroidal, potent SERD, in treatment-naïve patients with ER+ HER2- primary breast cancer awaiting curative intent surgery.

5. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105. [2022] This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.