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

NCT04307329 | Completed Phase 2

• 1 other identifier: N19MIM
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Response

  number of patients with partial response or complete response according to RECIST1.1

  to be assessed up to 120 months

Secondary Outcomes (4)

• Clinical Benefit

  to be assessed every 8 weeks up to 120 months

• Progression Free Survival

  assessed up to 120 months

• Overall survival

  assessed up to 120 months

• Toxicity; incidence of toxicity

  assessed every 2 weeks until 30 days after last study treatment

Study Arms (2)

Monalizumab + trastuzumab - low TILs (<5%)

EXPERIMENTAL

trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.

Biological: Monalizumab; Biological: Trastuzumab

Monalizumab + trastuzumab - high TILs (>=5%)

EXPERIMENTAL

trastuzumab 4 mg/kg and monalizumab 750 mg every two weeks.

Biological: Monalizumab; Biological: Trastuzumab

Interventions

Monalizumab BIOLOGICAL

Monalizumab 750 mg every two weeks

Monalizumab + trastuzumab - high TILs (>=5%); Monalizumab + trastuzumab - low TILs (<5%)

Trastuzumab BIOLOGICAL

Trastuzumab 4 mg/kg every two weeks

Monalizumab + trastuzumab - high TILs (>=5%); Monalizumab + trastuzumab - low TILs (<5%)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• AstraZeneca: collaborator

Study Sites (1)

NKI-AVL

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

monalizumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marleen Kok, MD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Two cohorts; high TILs (≥ 5%) and low (\< 5%) TILs
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Simon's two-stage minimax design

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 13, 2020
• Study Start: March 23, 2021
• Primary Completion: January 19, 2023
• Study Completion: March 23, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Locations

NL (1)