Study of Belzutifan Plus Fulvestrant for ER+/HER2- Metastatic Breast Cancer

Inclusion Criteria

• Have a diagnosis of estrogen receptor-positive (ER+)/HER2-negative breast cancer that is either locally advanced and cannot be surgically removed or has spread to other parts of the body.
• Have proof that the cancer has progressed during or after the last endocrine therapy.
• Provide additional tissue samples to confirm ER and HER2 status.
• Have received endocrine therapy in a noncurative setting and either:
  1. Experienced disease progression after 12 months or more of endocrine therapy combined with a CDK4/6 inhibitor.
  2. Received at least two lines of endocrine therapy, including a CDK4/6 inhibitor, which was stopped due to intolerance.
• Have a performance status score of 0 or 1, indicating full activity or some restriction in strenuous activities.
• Have recovered from side effects of previous cancer treatments to a mild level or baseline, except for certain hormone-related side effects or mild nerve damage.
• If positive for hepatitis B, have received antiviral therapy for at least four weeks and have an undetectable viral load before starting the study.

Exclusion Criteria

• Have breast cancer that can be treated with the intent to cure.
• Cannot receive any of the endocrine therapies (fulvestrant or exemestane).
• Have difficulty swallowing or absorbing oral medications due to conditions like severe nausea, vomiting, or digestive issues.
• Have advanced cancer that is rapidly worsening and could lead to life-threatening complications.
• Have active bleeding disorders or are taking blood thinners that affect vitamin K.
• Have a history of lung diseases like pneumonitis that required steroids or currently have lung disease.
• Have a known BRCA gene mutation and have been treated with PARP inhibitors before.
• Have previously received fulvestrant in any setting.
• Have received chemotherapy or PARP inhibitors for advanced cancer that cannot be cured.
• Have had recent radiotherapy for non-brain cancer or needed steroids for radiation side effects within 14 days of starting the study.
• Are taking strong medications that affect liver enzymes and cannot stop them during the study.
• Have received any cancer treatment or investigational drugs within four weeks before starting the study.
• Have had a live vaccine within 30 days before starting the study.
• Have active infections with both hepatitis B and C.
• Have serious heart conditions like recent heart attacks or severe heart failure.
• Have not fully recovered from major surgery or have ongoing surgical complications.