Phase Ib Study of Axatilimab in Combination With Olaparib in BRCA1/2 and PALB2- Associated Metastatic HER2-negative Breast Cancer

Recruiting now · Phase 1

Conditions studied: Breast Cancer, PALB2-Mutated Breast Carcinoma, HER2-negative Breast Cancer, BRCA1 Mutation, BRCA2 Mutation

In brief

This research is being done to evaluate the safety and tolerability of the new drug, axatilimab, in combination with olaparib (a standard of care treatment) in Breast Cancer 1/2 genes (BRCA 1/2) and PALB2 associated HER2-negative metastatic breast cancer. The names of the study drugs involved in this study are: * Axatilimab (a type of antibody) * Olaparib (a type of PARP inhibitor)

Key facts

Study ID

NCT06488378

Run by

Dana-Farber Cancer Institute

People needed

20

Starts

2024-08-13

Expected to finish

2029-03-01

Last updated by the study team

2025-08-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have histologically or cytologically confirmed metastatic or unresectable HER2 negative breast cancer, including HER2 low (IHC 2+/ISH-, IHC 1+). Any ER and PR expressions are permitted but must be known. Patients with hormone receptor (HR) positive disease, defined by either ER and/or PR positivity, must have progressed or are intolerant to all available endocrine therapy regimens, or not candidates to further endocrine therapy-based approaches.
• Documented germline or somatic mutation in BRCA1, BRCA2, or germline mutation in PALB2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Testing may be completed by any CLIA-certified laboratory.
• Participants must have evaluable or measurable disease per RECIST 1.1 criteria. NOTE: If the only site of measurable of disease has been previously irradiated, there must be evidence of post-radiation progression.
• Patients must have received no more than 2 prior lines of cytotoxic chemotherapy for metastatic disease. Antibody drug conjugates will count towards prior lines of cytotoxic chemotherapy, as well as checkpoint inhibitors. For the purposes of this study, prior treatment with hormonal therapy and non-hormonal targeted therapy, as well as the combination of an aromatase inhibitor and everolimus, are not counted as a prior cytotoxic therapy.
• Age ≥18 years.
• ECOG performance ≤ 2.
• Participants must meet the following organ and marrow function as defined below:
• leukocytes ≥ 3000/mcL
• absolute neutrophil count ≥ 1.5 x 109/L
• platelets ≥ 100 x 109/L
• total bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 2.5x × institutional ULN or ≤5 × institutional ULN for participants with documented liver metastases
• Creatinine clearance ≥ 51 mL/min (using Cockcroft-Gault equation)
• Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to registration.
• Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
• Hepatitis B screening tests are not required unless:
• Known history of HBV infection
• As mandated by local health authority
• Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
• Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to registration.
• Hepatitis C screening tests are not required unless:
• Known history of HCV infection
• As mandated by local health authority
• HIV-infected participants must have well-controlled HIV on ART, defined as:
• a. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening.

You may not qualify if…

• Clinical progression on a PARP inhibitor, or within 12 months of receipt of a PARP inhibitor, including but not limited to olaparib.
• Any previous treatment with CSF1R antibody.
• Patients who have had prior systemic chemotherapy, immune therapy, or investigational therapy within three weeks of initiation of protocol therapy. Endocrine therapy must have been discontinued at least 7 days prior to initiation of protocol therapy. Patients may receive bisphosphonates or denosumab during the study.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia, are excluded.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to axatilimab or olaparib.
• Participants receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP450 enzyme(s) are ineligible. This also includes strong or moderate CYP3A inhibitors and inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference.
• Participants with a QTcF of >470msec on screening ECG
• Patients with a history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
• Participants unable to swallow orally administered medication and participants with gastrointestinal disorders that are likely to interfere with absorption of the study medications in the opinion of the treating investigator (e.g. malabsorption syndrome or major stomach or bowel resections).
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of pneumonitis or ILD, or evidence of pneumonitis/ILD on baseline imaging
• Known active or latent tuberculosis
• Patients with major surgical procedure within 28 days prior to initiation of protocol therapy.

Where it is running

• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (enrolling)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.