Saruparib + Camizestrant for Breast Cancer

(EvoPAR-BR01 Trial)

Recruiting at 227 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers, CYP2B6 substrates

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 59 months

500 Participants Needed

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. ^{1 2 3 4 5}

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.

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

Treatment Details

Interventions

• Camizestrant
• Saruparib (AZD5305)

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

The phase II SERENA-2 trial indicates that camizestrant, an investigational oral selective estrogen receptor degrader, significantly prolongs progression-free survival compared to standard treatment with fulvestrant in postmenopausal women with advanced estrogen receptor-positive, HER2-negative breast cancer.

Camizestrant showed superior efficacy in specific patient subgroups, including those who had previously received a CDK4/6 inhibitor, had visceral metastases, or had ESR1 mutations, suggesting it may be particularly beneficial for these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second Oral SERD Shines in ER+ Breast Cancer. [2023]

Camizestrant, an oral selective estrogen receptor degrader (SERD), shows strong antitumor activity in estrogen receptor-positive (ER+) breast cancer, effectively degrading the estrogen receptor and inhibiting cancer cell growth in both wild-type and mutant models.

When combined with CDK4/6 inhibitors and PI3K/AKT/mTOR-targeted therapies, camizestrant enhances antitumor effects, making it a promising option for overcoming resistance to current endocrine therapies.

NCBI (Pubmed)

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. Lawson, M., Cureton, N., Ros, S., et al.[2023]

The SERENA-6 study is investigating the effectiveness of camizestrant, a next-generation oral selective estrogen receptor degrader, in patients with hormone-receptor-positive advanced breast cancer who have developed ESR1 mutations, which often lead to resistance against standard therapies.

The study aims to switch patients from aromatase inhibitors to camizestrant upon detecting ESR1 mutations in circulating tumor DNA, with the goal of improving progression-free survival and delaying the need for chemotherapy.

NCBI (Pubmed)

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. Turner, N., Huang-Bartlett, C., Kalinsky, K., et al.[2023]

In a presurgical study involving 46 women with ER+ HER2- breast cancer, AZD9496, an oral selective estrogen receptor degrader (SERD), demonstrated biological activity by reducing estrogen receptor (ER) levels, but was not superior to fulvestrant, the standard injectable SERD, in efficacy.

Both AZD9496 and fulvestrant effectively reduced progesterone receptor (PR) and Ki-67 levels, indicating their impact on tumor biology, but no new safety concerns were identified, suggesting that AZD9496 is safe to use.

NCBI (Pubmed)

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. Robertson, JFR., Evans, A., Henschen, S., et al.[2021]

In a phase II study involving 80 patients with early-stage triple-negative and BRCA1/2 mutation-associated breast cancer, the combination of iniparib, gemcitabine, and carboplatin resulted in a pathologic complete response rate of 36%, indicating its efficacy as a preoperative treatment.

The study found that higher homologous recombination deficiency loss of heterozygosity (HRD-LOH) scores were associated with better treatment responses, suggesting that this assay could help identify patients likely to benefit from the therapy, even those without BRCA1/2 mutations.

NCBI (Pubmed)

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. Telli, ML., Jensen, KC., Vinayak, S., et al.[2022]

References

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

Second Oral SERD Shines in ER+ Breast Cancer. [2023]

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]

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]

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]

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]