Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial (MIMOSA)
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Monalizumab
Trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring HER2 positive, Metastatic disease, Accessible lesion for study biopsies, Min 1, max 3 lines palliative treatment
Eligibility Criteria
Inclusion Criteria:
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
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 innmunosuppression (>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, Sjogren'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 autoinnmune disease
- prior treatment with immune checkpoint blockade or other forms of imnnunotherapy, such as but not limited to: anti-PD-(L)1, anti-PD-L2, anti-CTLA-4, anti-GITR or CD137/0X40 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
Sites / Locations
- NKI-AVL
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Monalizumab + trastuzumab - low TILs (<5%)
Monalizumab + trastuzumab - high TILs (>=5%)
Arm Description
trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
Outcomes
Primary Outcome Measures
Response
number of patients with partial response or complete response according to RECIST1.1
Secondary Outcome Measures
Clinical Benefit
number of patients with complete response, partial response or stable disease for more than 24 weeks according to RECIST1.1
Progression Free Survival
From date of registration until date of first documented progression or date of death, which ever comes first
Overall survival
From date of registration until date of death
Toxicity; incidence of toxicity
Adverse events will be graded according to NCI Common Toxicity Criteria version 5.0
Full Information
NCT ID
NCT04307329
First Posted
March 9, 2020
Last Updated
July 15, 2022
Sponsor
The Netherlands Cancer Institute
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT04307329
Brief Title
Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
Acronym
MIMOSA
Official Title
Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 23, 2021 (Actual)
Primary Completion Date
May 1, 2023 (Anticipated)
Study Completion Date
May 1, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this phase II clinical trial the efficacy of the combination of monalizumab and trastuzumab is assessed in patients with metastatic or locally incurable HER2-positive breast cancer
Detailed Description
In this phase II clinical trial with an explorative nature, the efficacy of the combination of monalizumab and trastuzumab is assessed in patients with metastatic or locally incurable HER2-positive breast cancer. Clinical efficacy will be assessed in patients with high stromal tumor-infiltrating lymphocytes (sTILs) or low sTILs in two separate cohorts (higher or equal to 5% versus lower than 5%). Since the combination of monalizumab and trastuzumab has not been administered before, dose limiting toxicities (DLTs) will be monitored throughout the trial using the Pocock-type boundary rules for continuous monitoring of toxicity in phase II trials.
In the first stage, 11 patients will be accrued per cohort. If there are 1 or fewer responses in these 11 patients, the study will be stopped. Otherwise, 8 additional patients will be accrued for a total of 19 patients.
The study will start with two cohorts (sTILs high and sTILs low), a total of 22 (2x11) patients will be included in the first stage. Dependent on the interim analysis (continuation of no cohorts, 1 or 2 cohorts), a maximum of 38 patients will be included.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
HER2 positive, Metastatic disease, Accessible lesion for study biopsies, Min 1, max 3 lines palliative treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Simon's two-stage minimax design
Masking
None (Open Label)
Masking Description
Two cohorts; high TILs (≥ 5%) and low (< 5%) TILs
Allocation
Non-Randomized
Enrollment
38 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Monalizumab + trastuzumab - low TILs (<5%)
Arm Type
Experimental
Arm Description
trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
Arm Title
Monalizumab + trastuzumab - high TILs (>=5%)
Arm Type
Experimental
Arm Description
trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
Intervention Type
Biological
Intervention Name(s)
Monalizumab
Intervention Description
Monalizumab 750 mg every two weeks
Intervention Type
Biological
Intervention Name(s)
Trastuzumab
Intervention Description
Trastuzumab 4 mg/kg every two weeks
Primary Outcome Measure Information:
Title
Response
Description
number of patients with partial response or complete response according to RECIST1.1
Time Frame
to be assessed up to 120 months
Secondary Outcome Measure Information:
Title
Clinical Benefit
Description
number of patients with complete response, partial response or stable disease for more than 24 weeks according to RECIST1.1
Time Frame
to be assessed every 8 weeks up to 120 months
Title
Progression Free Survival
Description
From date of registration until date of first documented progression or date of death, which ever comes first
Time Frame
assessed up to 120 months
Title
Overall survival
Description
From date of registration until date of death
Time Frame
assessed up to 120 months
Title
Toxicity; incidence of toxicity
Description
Adverse events will be graded according to NCI Common Toxicity Criteria version 5.0
Time Frame
assessed every 2 weeks until 30 days after last study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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 innmunosuppression (>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, Sjogren'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 autoinnmune disease
prior treatment with immune checkpoint blockade or other forms of imnnunotherapy, such as but not limited to: anti-PD-(L)1, anti-PD-L2, anti-CTLA-4, anti-GITR or CD137/0X40 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marleen Kok, MD
Organizational Affiliation
NKI-AvL
Official's Role
Principal Investigator
Facility Information:
Facility Name
NKI-AVL
City
Amsterdam
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
to be detemined
Learn more about this trial
Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
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