Trial Title:
Phase Ib Study of Axatilimab in Combination with Olaparib in BRCA1/2 and PALB2- Associated Metastatic HER2-negative Breast Cancer
NCT ID:
NCT06488378
Condition:
Breast Cancer
PALB2-Mutated Breast Carcinoma
HER2-negative Breast Cancer
BRCA1 Mutation
BRCA2 Mutation
Conditions: Official terms:
Breast Neoplasms
Olaparib
Conditions: Keywords:
Breast Cancer
PALB2-Mutated Breast Carcinoma
HER2-negative Breast Cancer
BRCA1 Mutation
BRCA2 Mutation
Metastatic HER2-negative Breast Cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Axatilimab
Description:
Humanized immunoglobulin G (IgG)4 monoclonal antibody, 1.3 mL sterile, preservative free
glass vials, via intravenous (into the vein) infusion per protocol.
Arm group label:
Axatilimab + Olaparib
Other name:
SNDX-6352
Other name:
Ab969.g2
Other name:
C24H23FN4O3
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Inhibitor of poly ADP ribose polymerase (PARP)1-3, 100 or 150 mg tablet, taken orally per
standard of care.
Arm group label:
Axatilimab + Olaparib
Other name:
Lynparza
Other name:
AZD2281
Other name:
KU-005943
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)
Detailed description:
This is a non-randomized, open-label, proof-of-concept phase 1 study to evaluate the
safety and tolerability of a drug known as Axatilimab in combination with the drug
Olaparib in BRCA1/2 and PALB2 associated HER2-negative breast cancer.
The U.S. Food and Drug Administration (FDA) has not approved axatilimab as a treatment
for any disease.
The FDA has approved olaparib as a treatment option for BRCA1/2 and PALB2 associated
HER2-negative breast cancer, and it is considered standard of care for those types of
breast cancer. The FDA has approved olaparib for metastatic (breast cancer that has
spread) BRCA1/2 associated HER2-negative breast cancer.
The research study procedures include screening for eligibility, study treatment
in-clinic visits, tumor biopsies, blood tests, Computerized Tomography (CT) scans,
Magnetic Resonance Imaging (MRI) scans, and electrocardiograms.
Participation in this research study is expected to last for as long as there is clinical
benefit and participants will be followed for a maximum of three years after finishing
study treatment.
It is expected that about 16-20 people will take part in this research study.
Incyte Corporation is funding this research study and providing Axatilimab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- b. Participants on ART must have achieved and maintained virologic suppression
defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of
detection) using the locally available assay at the time of screening and for
at least 12 weeks before screening.
- c. It is advised that participants must not have had any AIDS-defining
opportunistic infections within the past 12 months.
- d. Participants on ART must have been on a stable regimen, without changes in
drugs or dose modification, for at least 4 weeks before study entry (Day 1) and
agree to continue ART throughout the study.
- e. The combination ART regimen must not contain any antiretroviral medications
that interact with CYP3A4 inhibitors/inducers/substrates
(https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-
drug-interactions-table-substrates-inhibitors-and-inducers)
- Ability to swallow and retain oral study medication
- Patients with a history of treated central nervous system (CNS) metastases are
eligible, provided they meet all of the following criteria:
- Disease outside the CNS is present
- No clinical evidence of progression in the CNS since completion of CNS-directed
therapy
- Minimum of 2 weeks between completion of radiotherapy and Cycle 1 Day 1
- Recovery from significant (≥ Grade 3) acute toxicity with no requirement for
escalating doses of corticosteroid over the 7 days prior to treatment start.
- Participants with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial.
- Female participants must be postmenopausal or must have a negative serum pregnancy
test performed during screening. Postmenopausal is defined as:
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal
treatments
- Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the
postmenopausal range for women under 50.
- Radiation-induced oophorectomy with last menses >1 year ago
- Chemotherapy-induced menopause with >1 year interval since last menses
- Bilateral oophorectomy (with or without hysterectomy) or tubal ligation at
least six weeks ago
- The effects of axatilimab and olaparib on the developing human fetus are unknown.
For this reason, women of child-bearing potential and men who are sexually active
with WOCBP must agree to use adequate contraception for the duration of study
participation and for 4 months after discontinuation of treatment.
- Participants must be willing to undergo 3 research biopsies: at baseline, after 2
weeks of olaparib monotherapy, and after 2 cycles of combination therapy. If biopsy
is not feasible or safe, OR if the only area accessible to biopsy is also the only
site of measurable disease per RECIST 1.1 criteria, permission must be obtained from
the DFCI sponsor- investigator to forgo the mandatory research biopsies. Formal
eligibility exception would not be required in these circumstances.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Filipa Lynce, MD
Phone:
617-632-2335
Email:
Filipa_Lynce@DFCI.HARVARD.EDU
Contact backup:
Last name:
Filipa Lynce, MD
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Filipa Lynce, MD
Phone:
617-632-2335
Email:
Filipa_Lynce@DFCI.HARVARD.EDU
Contact backup:
Last name:
Filipa Lynce, MD
Start date:
August 13, 2024
Completion date:
March 1, 2029
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06488378
