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)
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.
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.
Single group
Axatilimab
DrugHumanized immunoglobulin G (IgG)4 monoclonal antibody, 1.3 mL sterile, preservative free glass vials, via intravenous (into the vein) infusion per protocol.
Olaparib
DrugInhibitor of poly ADP ribose polymerase (PARP)1-3, 100 or 150 mg tablet, taken orally per standard of care.
Maximum Tolerated Dose (MTD)
MTD is determined by Bayesian optimal interval (BOIN) design, where the target toxicity rate for the MTD is 0.25 and the maximum sample size is 20.
Recommended Phase 2 Dose (RP2D)
If the MTD is identified as 3mg/kg, we will complete enrollment of 10 pts at the 1 mg/kg dose level, to determine if there is biological effectiveness (and clinical efficacy) at the lower dose level.
Objective Response Rate (ORR)
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Median Progression Free Survival (PFS)
PFS based on Kaplan-Meier method is defined as the time from registration to the earlier of progression (per RECIST 1.1) or death due to any cause. Participants alive without disease progression are censored at data of last disease evaluation. Deaths that occur within the time frame of the disease assessment period will count towards the PFS estimate. Deaths that occur outside of this assessment period will be censored at date of last disease evaluation.
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Dana-Farber Cancer Institute
Lead sponsor
Incyte Corporation
Collaborator
