Treating HER2-negative, Metastatic Breast Cancer with a BRCA or PALB2 Mutation Using a New Drug, Axatilimab Combined with Olaparib

About the Study

This clinical trial is studying a new combination of drugs to treat metastatic, HER2-negative or HER2-low breast cancer in people with an inherited mutation or tumor mutation in BRCA1, BRCA2 or PALB2. The study is looking at whether adding a new targeted therapy drug called axatilimab to treatment with the PARP inhibitor olaparib (Lynparza) will improve outcomes in people with metastatic breast cancer. 

What the Study Involves

All participants will receive the combination of both drugs, olaparib and axatilimab. 

Treatment will be given in 28-day cycles. 

Cycle 1 through Cycle 2:

• Day 1 and 15:
  • participants will receive axalitimab as an intravenous (iv) injection.
• Days 1 through 28:
  • participants will take olaparib orally 2 times daily, 12 hours apart.

Cycle 3 through End of Treatment:

• Days 1 and 15:
  • participants will receive axalitimab as an intravenous (iv) injection.
• Days 1 through 28:
  • participants will take olaparib orally 2 times daily, 12 hours apart.
• End of Treatment Visit with imaging
• Follow Up: Every 6 months for 3 years. Imaging will be every 10 weeks.

Biopsies

Participants will undergo repeat biopsies of their cancer:

• at the start of the study.
• after two weeks of olaparib.
• at the end of cycle 2.

Imaging

Participants will undergo repeat imaging to make sure that their cancer is not getting worse:

• at the start of the study.
• every 8 weeks during the study.
• at the end of treatment. 
• every 10 weeks for up to 3 years. 

Follow-up visits

Follow-up visits will continue every 6 months for 3 years. 

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

• have HER2-negative or HER2-low breast cancer.
• have hormone receptor positive (HR-positive) or hormone receptor negative (HR-negative) cancers.  
  • participants with hormone receptor HR-positive disease must not be eligible for hormone therapy (due to cancer progression or other factors that make them in)
• have an inherited mutation in BRCA1, BRCA2, or PALB2 or a tumor mutation in BRCA1 or BRCA2.
• have evidence of cancer that can be measured by imaging to track whether or not cancer is responding to treatment. 
• have received at least two prior treatments that included chemotherapy, immunotherapy or a type of targeted therapy known as an antibody-drug conjugate. 
• must be willing to undergo 3 separate research biopsies.  

Additional criteria:

•  people with brain or central nervous system spread may participate if:
  • they also have spread to other parts of the body that can be measured with imaging. 
  • they have not had progression of cancer in the brain or central nervous system after treatment for that spread.
• people who are infected with HIV or Hepatitis B or C may participate if their disease is controlled with medication. 
• prior treatment with a PARP inhibitor is allowed as long as the cancer did not get worse while on, or up to a year after PARP inhibitor treatment.
• must be at least 4 weeks out from major surgery, 3 weeks out from receiving chemotherapy, targeted therapy or immunotherapy and1 week out from receiving hormone therapy.  

Please see ClinicalTrials.gov for a more complete list of eligibility requirements. 

• people under age 18.
• people still experiencing side effects from previous treatment. 
• people with other conditions such as high blood pressure, heart disease, infection that is not controlled with medication. 

This is not a full list of exclusions. Please see ClinicalTrials.gov for a more complete list.