Clinical Trials /

Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial

NCT04307329

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial
  • Official Title: Monalizumab and Trastuzumab In Metastatic HER2-pOSitive breAst Cancer: MIMOSA-trial

Clinical Trial IDs

  • ORG STUDY ID: N19MIM
  • NCT ID: NCT04307329

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
MonalizumabMonalizumab + trastuzumab - high TILs (>=5%)
TrastuzumabMonalizumab + trastuzumab - high TILs (>=5%)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Monalizumab + trastuzumab - low TILs (<5%)Experimentaltrastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
  • Monalizumab
  • Trastuzumab
Monalizumab + trastuzumab - high TILs (>=5%)Experimentaltrastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.
  • Monalizumab
  • Trastuzumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response
Time Frame:to be assessed up to 120 months
Safety Issue:
Description:number of patients with partial response or complete response according to RECIST1.1

Secondary Outcome Measures

Measure:Clinical Benefit
Time Frame:to be assessed every 8 weeks up to 120 months
Safety Issue:
Description:number of patients with complete response, partial response or stable disease for more than 24 weeks according to RECIST1.1
Measure:Progression Free Survival
Time Frame:assessed up to 120 months
Safety Issue:
Description:From date of registration until date of first documented progression or date of death, which ever comes first
Measure:Overall survival
Time Frame:assessed up to 120 months
Safety Issue:
Description:From date of registration until date of death
Measure:Toxicity; incidence of toxicity
Time Frame:assessed every 2 weeks until 30 days after last study treatment
Safety Issue:
Description:Adverse events will be graded according to NCI Common Toxicity Criteria version 5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:The Netherlands Cancer Institute

Trial Keywords

  • HER2 positive
  • Metastatic disease
  • Accessible lesion for study biopsies
  • Min 1, max 3 lines palliative treatment

Last Updated

March 12, 2020