Studying a New PARP Inhibitor and Hormonal Therapy to Treat HER2-negative, HR-positive Metastatic Breast Cancer with a BRCA1, BRCA2, or PALB2 Mutation (EvoPAR BR01)

About the Study

EvoPAR-BR01 is studying two investigational drugs for treating HER2-negative, HR-positive, metastatic breast cancer patients with an inherited or tumor BRCA1, BRCA2 or PALB2 mutation. The study is enrolling patients who have not yet received treatment for metastatic breast cancer. Saruparib is a new PARP1 inhibitor (a type of targeted therapy). Camizestrant is an estrogen receptor degrader (a type of hormonal therapy). Participants will be randomly assigned to one of three groups. Each group will receive a different combination of treatments to learn which combination leads to the best survival and fewest side effects. 

What the Study Involves

Participants will be assigned by chance to one of three groups:

Group 1: 

• Saruparib orally plus Camizestrant orally.
  • Both drugs are investigational agents not yet approved by the FDA. 

Group 2: 

• CDK4/6 inhibitor orally plus hormonal therapy (oral or intramuscular depending on the drug chosen by the patient's oncologist).
  • CDK4/6 inhibitors are a type of targeted therapy commonly used for metastatic breast cancer. Participants' oncologist will choose from one of the three FDA-approved agents: Abemiciclib (Verzenio), Palbociclib (Ibrance), or Ribociclib (Kisqali).
  • Participants' oncologist will choose from the following FDA-approved agents: Fulvestrant (Faslodex) intramuscular injection, Letrozole (Femara) orally, Anastrozole (Arimidex) orally, or Exemestane (Aromasin) orally.

Group 3:

• CDK4/6 inhibitor orally plus Camizestrant orally. 

Participants will be monitored over the course of the study for response to treatment and side effects. Participants will continue to receive treatment unless the cancer gets worse, they experience intolerable side effects or they decide to withdraw from the study. 

People with metastatic breast cancer may be eligible if they meet all of the following: 

• have HR-positive, HER2-negative metastatic breast cancer.
• have an inherited, and/or tumor mutation in BRCA1, BRCA2 or PALB2. 
• have not received any treatment in the metastatic setting, other than hormonal therapy within 28 days of starting the study. 

Patients with brain or central nervous system involvement may be eligible if they have received definitive local therapy, are asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to study start. At least 2 weeks must have elapsed since completion of brain radiotherapy before enrollment.

People who: 

• have received treatment in the metastatic setting except for hormonal therapy for 28 days or less before joining the study.
• have brain or central nervous system spread wth symptoms or requiring steroids for management.
• have a bleeding disorder.
• have uncontrolled disease or infection.
• have a history of diagnosis with another type of cancer.