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

NCT06488378 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24-155
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

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)

Conditions

Breast Cancer; PALB2-Mutated Breast Carcinoma; HER2-negative Breast Cancer; BRCA1 Mutation; BRCA2 Mutation

Keywords

Breast Cancer; PALB2-Mutated Breast Carcinoma; HER2-negative Breast Cancer; BRCA1 Mutation; BRCA2 Mutation; Metastatic HER2-negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 4 weeks

• 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.

  Up to 4 weeks

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  Up to 6 months

• Median Progression Free Survival (PFS)

  Up to 6 months

Study Arms (1)

Axatilimab + Olaparib

EXPERIMENTAL

A Bayesian Optimal Interval design will be used to establish the maximum tolerated dose of Axatilimab. Dose reduction and escalation will be per protocol. Participants will complete: * Baseline visit, tumor biopsy, and imaging * Imaging every 8 weeks * Window Phase: --Predetermined dose of Olaparib 2x daily, taken 12 hours apart for 14 days * Combination Treatment Phase: * Cycle 1 through Cycle 2: * Day 1 of 28 day cycle: Tumor biopsy * Days 1 and 15 of 28 day Cycle: Predetermined dose of Axalitimab 1x daily * Days 1 through 28 of 28 day cycle Predetermined dose of Olaparib 2x daily, 12 hours apart * Tumor biopsy after two weeks of Olaparib and at the end of Cycle 2 * Cycle 3 through End of Treatment: * Days 1 and 15 of 28 Day Cycle: Predetermined dose of Axalitimab 1x daily * Predetermined dose of Olaparib 2x daily, taken 12 hours apart * End of Treatment Visit with imaging * Follow Up: Every 6 months for 3 years. Imaging will be every 10 weeks.

Drug: Axatilimab; Drug: Olaparib

Interventions

Axatilimab DRUG

Humanized immunoglobulin G (IgG)4 monoclonal antibody, 1.3 mL sterile, preservative free glass vials, via intravenous (into the vein) infusion per protocol.

Also known as: SNDX-6352, Ab969.g2, C24H23FN4O3

Axatilimab + Olaparib

Olaparib DRUG

Inhibitor of poly ADP ribose polymerase (PARP)1-3, 100 or 150 mg tablet, taken orally per standard of care.

Also known as: Lynparza, AZD2281, KU-005943

Axatilimab + Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Incyte Corporation: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

axatilimab; olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Filipa Lynce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filipa Lynce, MD

CONTACT

617-632-2335; filipa_lynce@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: July 5, 2024
• Study Start: August 13, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2029
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)