CU Anschutz Cancer Center Leads Global Phase 3 Trial Testing Novel PARP Inhibitor Combination for BRCA-Mutated Metastatic Breast Cancer
Key Insights
CU Anschutz Cancer Center is the only Rocky Mountain site recruiting for the global EvoPAR-Breast01 phase 3 trial, testing AstraZeneca's investigational PARP1 (search) inhibitor saruparib combined with selective estrogen receptor (search) degrader camizestrant.
The trial targets patients with HR-positive, HER2-negative metastatic breast cancer (search) carrying BRCA1 (search), BRCA2 (search), or PALB2 (search) mutations, a population that typically has poor outcomes with standard CDK4/6 inhibitor therapy.
The randomized three-arm study compares the novel combination against standard-of-care treatments, aiming to enroll 500 patients worldwide to determine if the investigational approach can delay cancer progression more effectively than current therapies.
The University of Colorado Anschutz Cancer Center (search) has become the sole Rocky Mountain recruitment site for a global phase 3 clinical trial investigating a novel therapeutic combination for patients with advanced breast cancer carrying specific genetic mutations. The EvoPAR-Breast01 trial, sponsored by AstraZeneca, is testing whether a new generation PARP1 (search) inhibitor combined with an innovative endocrine therapy can outperform current standard treatments.
Dr. Marie Wood, medical director of the cancer center's Hereditary Cancer Program and professor of medicine in the Division of Medical Oncology, serves as the site principal investigator. Wood recently received a five-year Research Specialist Award (R50) from the National Cancer Institute to expand cancer clinical trial scope.
Targeting a High-Risk Patient Population
The trial specifically enrolls patients with HR-positive, HER2-negative metastatic breast cancer (search) who carry mutations in tumor-suppressor genes BRCA1 (search), BRCA2 (search), or PALB2 (search). This breast cancer subtype represents approximately 70% of all breast cancer cases, but patients with these genetic mutations "tend to have overall poor outcomes," according to Wood.
Current standard care for metastatic HR+/HER2- breast cancer involves endocrine therapy combined with CDK4/6 inhibitors (search). However, Wood notes that data shows CDK4/6 inhibitors can be less effective when BRCA or PALB2 (search) mutations are present, creating an urgent need for alternative therapeutic approaches.
Novel Therapeutic Mechanisms
The investigational treatment saruparib represents a new generation of PARP1 (search) inhibitors designed to block enzymes that help repair DNA damage in cancer cells, forcing cell death. The combination partner, camizestrant, is a selective estrogen receptor (search) degrader (SERD) that breaks down estrogen receptors on cancer cell surfaces, also leading to cell death.
Both experimental drugs are oral medications, allowing trial participants to receive treatment without repeated visits to the cancer center. "We will be partnering with their community provider on this," Wood explained.
Three-Arm Randomized Design
The EvoPAR trial randomly assigns participants to one of three treatment groups:
- Arm 1: Saruparib combined with camizestrant (investigational combination)
- Arm 2: FDA-approved standard-of-care combination of CDK4/6 inhibitor plus standard endocrine therapy
- Arm 3: CDK4/6 inhibitor combined with camizestrant
"We will be answering if the investigational arm (Arm 1) is superior to standard of care treatment. Superior is defined by cancer taking longer to progress," Wood stated. Participants continue treatment until cancer progression, intolerable side effects, or voluntary withdrawal.
Global Recruitment Challenges
Finding eligible patients presents significant challenges due to the specific criteria requirements, necessitating multiple international sites across North and South America, Europe, Asia, and Australia. Wood has been actively promoting awareness through organizations including FORCE (Facing Our Risk of Cancer Empowered), a national hereditary cancer advocacy group, and oncologists throughout Colorado.
AstraZeneca covers genetic testing costs for potential participants. The study aims to enroll approximately 500 patients worldwide with several years of follow-up planned.
The cancer center's participation in this large-scale global study demonstrates "our ability to attract industry partners to do novel therapeutic strategies," Wood noted, highlighting the institution's growing reputation in innovative cancer research.