Monalizumab and trastuzumab In Metastatic HER2-pOStive breAst cancer: MIMOSA-trial
- Conditions
- MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000849-14-NL
- Lead Sponsor
- KI-AV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 38
• Histologically confirmed HER2-positive (immunohistochemistry 2+ with SISH amplification or 3+ with or without SISH amplification) breast cancer. HER2-positivity must have been assessed on 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
• 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. 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the activity (as measured by objective response rate by RECIST1.1) of monalizumab and trastuzumab in patients with metastatic HER2-positive breast cancer with high or low stromal tumor-infiltrating lymphocyte levels (higher or equal to 5% versus lower than 5%). ;Secondary Objective: Secondary Objectives:<br>• To evaluate activity (as measured by objective response rate by RECIST1.1) in all included patients<br>• To evaluate progression-free survival according to RECIST1.1<br>• To evaluate overall survival<br>• To evaluate the safety of monalizumab and trastuzumab as the percentage of patients with toxicity and immune-related adverse events <br>;Primary end point(s): objective response rate (partial response or complete response) according to RECIST1.1;Timepoint(s) of evaluation of this end point: Every 8 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Clinical benefit (complete response, partial response or stable disease for more than 24 weeks) according to RECIST1.1 <br>• Progression-free survival according to RECIST1.1 <br>• Overall survival <br>• Presence of toxicity and immune-related adverse events (classified according to CTCAE v5.0)<br>;Timepoint(s) of evaluation of this end point: Response; every 8 weeks until progression of disease<br>Survival; until death from any cause<br>Toxicity; every 2 weeks until 30 days after last treatment