Breast CancerPhase 2MIMOSANCT04307329
Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
A Phase 2 study testing Monalizumab and Trastuzumab in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Monalizumab and Trastuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Mar 2021to 23 Mar 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Monalizumab, Trastuzumab
- Keywords
- HER2 positive, Metastatic disease, Accessible lesion for study biopsies, Min 1, max 3 lines palliative treatment
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MonalizumabBiological
Monalizumab 750 mg every two weeks
TrastuzumabBiological
Trastuzumab 4 mg/kg every two weeks
| Study group | Role | What they receive |
|---|---|---|
| Monalizumab + trastuzumab - low TILs (<5%) | Experimental | trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks. Receives: Biological: Monalizumab; Biological: Trastuzumab |
| Monalizumab + trastuzumab - high TILs (>=5%) | Experimental | trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks. Receives: Biological: Monalizumab; Biological: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response
number of patients with partial response or complete response according to RECIST1.1
Measured: to be assessed up to 120 months
Secondary outcomes (4)
Clinical Benefit
number of patients with complete response, partial response or stable disease for more than 24 weeks according to RECIST1.1
Measured: to be assessed every 8 weeks up to 120 months
Progression Free Survival
From date of registration until date of first documented progression or date of death, which ever comes first
Measured: assessed up to 120 months
Overall survival
From date of registration until date of death
Measured: assessed up to 120 months
Toxicity; incidence of toxicity
Adverse events will be graded according to NCI Common Toxicity Criteria version 5.0
Measured: assessed every 2 weeks until 30 days after last study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2020
- Study start23 Mar 2021
- Primary completion19 Jan 2023
- Study completion23 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Simon's two-stage minimax design
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Marleen Kok, MD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04307329
- Sponsor's protocol ID
- N19MIM
- Acronym
- MIMOSA
- Status last verified
- Oct 2024
- First submitted
- 9 Mar 2020
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: to be detemined
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
- ClinicalTrials.gov ID
- NCT04307329
- Acronym / sponsor ID
- MIMOSA / N19MIM
- Conditions
- Breast Cancer
- Keywords
- HER2 positive, Metastatic disease, Accessible lesion for study biopsies, Min 1, max 3 lines palliative treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 19 Jan 2023 (actual)
- Study completion
- 23 Mar 2024 (actual)
- First posted
- 13 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Simon's two-stage minimax design
| Arm | Type | Receives |
|---|---|---|
| Monalizumab + trastuzumab - low TILs (<5%) | Experimental | Biological: Monalizumab, Biological: Trastuzumabtrastuzumab 4 mg/kg and monalizumab 750 mg every two weeks. |
| Monalizumab + trastuzumab - high TILs (>=5%) | Experimental | Biological: Monalizumab, Biological: Trastuzumabtrastuzumab 4 mg/kg and monalizumab 750 mg every two weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MonalizumabMonalizumab 750 mg every two weeks | Biological | Monalizumab + trastuzumab - high TILs (>=5%), Monalizumab + trastuzumab - low TILs (<5%) |
| TrastuzumabTrastuzumab 4 mg/kg every two weeks | Biological | Monalizumab + trastuzumab - high TILs (>=5%), Monalizumab + trastuzumab - low TILs (<5%) |
Primary outcome
Response
Time frame: to be assessed up to 120 months
number of patients with partial response or complete response according to RECIST1.1
4 secondary outcomes
Clinical Benefit
Time frame: to be assessed every 8 weeks up to 120 months
Progression Free Survival
Time frame: assessed up to 120 months
Overall survival
Time frame: assessed up to 120 months
Toxicity; incidence of toxicity
Time frame: assessed every 2 weeks until 30 days after last study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- Individual participant dataSharing planned: Undecided. to be detemined
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marleen Kok, MD principal investigator
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Monalizumab and Trastuzumab in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response (time frame: to be assessed up to 120 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2024.