Monalizumab and trastuzumab In Metastatic HER2-pOStive breAst cancer: MIMOSA-trial

Phase 2

Completed

Conditions: Breast cancer
HER2 positive
10006291

Registration Number: NL-OMON52889

Lead Sponsor: ederlands Kanker Instituut

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 19

Inclusion Criteria

• Histologically confirmed HER2-positive (immunohistochemistry 2+ with SISH
amplification or 3+ reagrdless of SISH amplification) breast cancer.
HER2-positivity must have been assessed on a baseline study biopsy of a
metastatic lesion.
• Histological or cytological confirmed locally incurable or metastatic disease
• Accessible lesion for study biopsies.
• Administration of at least one line of palliative treatment with documented
progression and a maximum of three lines of palliative chemotherapy in
combination with HER2 targeting agents (TDM-1 is considered one line of
palliative treatment). Trastuzumab in combination with endocrine treatment is
not defined as one line of treatment.
• Documented progression during previous trastuzumab-based therapy
• Measurable disease according to RECIST1.1 (at least one target lesion)
• Left ventricular ejection fraction of 50% or higher
• WHO performance status of 0 or 1
• No signs of a visceral crisis
• Signed written informed consent
- Subjects with brain metastases are eligible if they have been treated,
asymptomatic and there is no magnetic resonance imaging (MRI) evidence of
progression for at least 4 weeks prior to study registration. There must also
be no requirement for immunosuppressive doses of systemic corticosteroids (> 10
mg/day prednisone equivalents) for at least 2 weeks prior to study drug
administration

Exclusion Criteria

• uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, symptomatic congestive heart failure, unstable angina pectoris
• known leptomeningeal disease localization
• history of having received other anticancer therapies within 2 weeks of start
of the study drug
• history of immunodeficiency, autoimmune disease, conditions requiring
immunosuppression (>10 mg daily prednisone equivalents) or chronic infections.
Subjects with vitiligo, diabetes mellitus type I on a stable insulin regimen,
psoriasis not requiring systemic treatment or resolved childhood asthma/atopy
would be an exception to this rule. Subjects that require intermittent use of
bronchodilators, inhaled steroids, or local steroid injections will not be
excluded from the study. Subjects with hypothyroidism stable on hormone
replacement, Sjøgren*s syndrome or conditions not expected to recur in the
absence of an external trigger will not be excluded from the study. In
addition, subjects with Graves* disease stable on hormone replacement will also
not be excluded from the study. Adrenal replacement doses >10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease
• prior treatment with immune checkpoint blockade or other forms of
immunotherapy, such as but not limited to: anti-PD-(L)1, anti-PD-L2,
anti-CTLA-4, anti-GITR or CD137/OX40 agonists
• prior treatment with HER2-based vaccines
• live vaccine within two weeks prior to start of the study, at any time during
the study or within 5 months following the last dose of monalizumab.
Inactivated vaccines, such as the seasonal flu vaccination, are allowed
• history of clinically significant or uncontrolled cardiac disease, including
congestive heart failure (New York Heart Association functional classification
>=3), angina, myocardial infarction within 12 months prior to study treatment or
ventricular arrhythmia.
• active other cancer
• positive test for hepatitis B surface virus surface antigen (HBsAg) or
hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic
infection.
• allogeneic stem cell or organ transplantation, HIV or active tuberculosis
• history of uncontrolled serious medical or psychiatric illness
• Presence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule
• current pregnancy or breastfeeding. Women of childbearing potential (WOCBP*)
must use adequate contraceptive protection. WOCBP must have a negative serum or
urine pregnancy test

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Objective:<br /><br>To determine the activity (as measured by objective response rate by RECIST1.1)<br /><br>of monalizumab and trastuzumab in patients with metastatic HER2-positive breast<br /><br>cancer. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Objectives:<br /><br>• To evaluate activity (as measured by objective response rate by RECIST1.1) in<br /><br>all included patients<br /><br>• To evaluate progression-free survival according to RECIST1.1<br /><br>• To evaluate overall survival<br /><br>• To evaluate the safety of monalizumab and trastuzumab as the percentage of<br /><br>patients with toxicity and immune-related adverse events </p><br>