Active Cancer NIHR-supported project Digestion, Kidneys & Other Organs

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant compared with Physician’s Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients with BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified) Advanced Breast Cancer

In plain English

AI plain-English summary

A 500-patient global trial is testing whether a new drug combination can delay cancer progression longer than standard therapy for people with inherited BRCA1, BRCA2, or PALB2 mutations and a common form of advanced breast cancer. These mutations impair the body’s ability to repair DNA damage, making tumours vulnerable to PARP1 inhibitors like saruparib. Current first-line treatment—a CDK4/6 inhibitor plus hormone therapy—works for many patients, but resistance eventually develops. The trial compares saruparib plus camizestrant (which blocks oestrogen signalling) against the standard regimen, and also against camizestrant plus a CDK4/6 inhibitor. The goal is to see whether the PARP1-inhibitor combination buys more time before the disease worsens. If saruparib plus camizestrant proves superior, it could become a new first-line option for this genetically defined patient group. That would shift clinical practice away from a one-size-fits-all approach toward targeted therapy matched to a tumour’s DNA repair defect—potentially extending the period during which patients maintain quality of life without needing more toxic treatments. The trial is not fundamental science; it is a direct test of a commercially developed drug regimen in a specific, actionable patient population.

View original technical description
The primary objective of this study is to demonstrate the superiority of saruparib + camizestrant relative to physician’s choice CDK4/6i + ET, by assessment of PFS. The purpose of this study is to learn more about whether saruparib combined with another study drug called camizestrant, works better for participants with advanced breast cancer when compared to current standard of care treatment: a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor combined with hormone therapy.Saruparib is a type of drug known as a PARP1 inhibitor (polyadenosine di-phosphate ribose polymerase inhibitor). Approximately 500 participants will take part in this study at multiple different locations around the world.Participants will receive treatment with saruparib plus camizestrant or physician’s choice CDK4/6i plus ET or physician’s choice CDK4/6i plus camizestrant, until BICR-confirmed disease progression by RECIST v1.1 or unacceptable toxicity occurs, or the participant withdraws consent. Participants will be allocated to one of three different treatment regimens in this study: • Arm 1: Saruparib with camizestrant • Arm 2: Physician's choice CDK4/6 inhibitor with hormone therapy • Arm 3: Physician's choice CDK4/6 inhibitor with camizestrant. Patients will take the study drug once a day during each cycle (28 days long) and they will be required to go to the study site every 2 weeks for the first 12 weeks after they start study treatment, and then every 4 weeks until they stop taking both study drugs.Participants will have the following visits: Bio-marker testing Screening Visit Cycle 1, Day 1 Cycle 1, Day 15 Cycle 2, Day 1 Cycle 2, Day 15 Cycle 3, Day 1 Cycle 3, Day 15 Cycles 4+, Day 1 of every cycle Treatment Discontinuation Disease Progression Safety FU & Survival FU Tumour imaging/ measurement (RECIST v1.1) from randomisation until RECIST v1.1-defined radiographic progression (by BICR).

Researchers

Karen McAdam (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant compared with Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients with BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified) Advanced Breast Cancer
A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant compared with Physician’s Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients with BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)
CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients with ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence of Disease
CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients with ER+/HER2- Early Breast Cancer and an Intermediate-High or High Risk of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence of Disease (CAMBRIA-2)
A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor (Palbociclib or Abemaciclib) vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole) + CDK4/6 Inhibitor in HR+/HER2- MBC Patients with Detectable ESR1 Mutation Without Disease Progression During 1L Treatment with Aromatase Inhibitor + CDK4/6 Inhibitor.

Original classification

Cancer

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