Phase 2 study of MCLA-128-based combinations in metastatic breast cancer (MBC): MCLA-128/trastuzumab/chemotherapy in HER2-positive MBC and MCLA-128/endocrine therapy in estrogen receptor positive and low HER2 expression MBC - MCLA-128-CL02

Merus N.V.0 个研究点目标入组 70 人开始时间: 待定最近更新: 2024年4月15日

适应症

试验速览

阶段: 2 期
状态: 已完成
发起方: Merus N.V.
入组人数: 70

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

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研究设计

研究类型: Observational invasive

入排标准

年龄范围: 18 至 99（—）

入选标准

•1. Signed informed consent before initiation of any study procedures.
•2. Women with histologically or cytologically confirmed breast cancer with
•evidence of metastatic or locally advanced disease not amenable to any local
•therapy with curative intent:
•2.1 Cohort 1 (MCLA-128 + trastuzumab ± vinorelbine)
•a. Documented HER2 overexpression/amplification, defined as
•immunohistochemistry (IHC) 3+ positive, or IHC 2+ combined with positive
•fluorescence in situ hybridization (FISH), based on local analysis on the most
•recent tumor biopsy (preferably metastatic, otherwise primary), either fresh or
•archival collected within 24 months before screening..
•b. Documented disease progression (by investigator assessment) on up to a
•maximum of 5 lines of HER2-directed therapy administered in the metastatic
•setting, and have progressed on the most recent line. Trastuzumab, pertuzumab
•and an HER2 antibody drug conjugate (e.g. T-DM1) must have been previously
•administered in any sequence and in any setting.
•2.2 Cohort 2 (MCLA-128 + endocrine therapy)
•a. Documented hormone receptor positive status (estrogen receptor positive
•[ER+] and/or progesterone receptor positive [PR+]), defined as >= 1% positive
•stained cells by local standards, based on local analysis on the most recent
•tumor biopsy
•b. Documented low-level HER2 expression, defined as IHC HER2 1+, or IHC
•HER2 2+ combined with negative FISH, based on local testing on a fresh tumor
•biopsy or an archival biopsy collected within 24 months before screening
•(preferably metastatic otherwise primary).
•c. No more than 3 lines of prior endocrine therapy (aromatase inhibitor or
•fulvestrant) for metastatic disease, with radiologically documented disease
•progression on the last line, after at least 12 weeks of therapy.
•d. Progression on a cyclin-dependent kinase inhibitor.
•e. No more than two previous chemotherapy regimen for advanced/metastatic
•Note: Pre/peri-menopausal women can be enrolled if amenable to be treated with
•the LHRH agonist goserelin. Such patients must have commenced treatment with
•goserelin or an alternative LHRH agonist at least 4 weeks prior to study entry,
•and patients who received an alternative LHRH agonist prior to study entry must
•switch to goserelin for the duration of the trial.
•3. In Cohort 1, patients must have at least one lesion with measurable disease
•as defined by RECIST version 1.1. In Cohort 2, patients must have at least one
•lesion with measurable disease as defined by RECIST version 1.1. Patients with
•bone-only disease are eligible, even in the absence of measurable disease.
•Patients with bone-only disease must have lytic or mixed lesions (lytic +
•sclerotic). For Cohort 2, imaging documenting progression on the last line of
•hormone therapy must be available for central review..
•4. Age >= 18 years at signature of informed consent.
•5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
•6. Life expectancy of >= 12 weeks, as per investigator.
•7. Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram (ECHO) or
•multiple gated acquisition scan (MUGA).
•8. Adequate organ function:
•a. Absolute neutrophil count (ANC) >= 1.5 X 109/L
•b. Hemoglobin >= 9 g/dL
•c. Platelets >= 100 x 109/L
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排除标准

•1. Central nervous system metastases that are untreated or symptomatic, or
•require radiation, surgery, or continued steroid therapy to control symptoms
•within 14 days of study entry.
•2. Known leptomeningeal involvement.
•3. Advanced/metastatic, symptomatic, visceral spread, with a risk of
•life-threatening complications in the short term (including patients with
•massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary
•lymphangitis, and over 50% liver involvement).
•4. Participation in another interventional clinical trial or treatment with any
•investigational drug within 4 weeks prior to study entry.
•5. Any systemic anticancer therapy within 3 weeks of the first dose of study
•treatment. For cytotoxic agents that have major delayed toxicity, e.g.
•mitomycin C and nitrosoureas, or anticancer immunotherapies, a washout period
•of 6 weeks is required. For patients in Cohort 2, this does not apply to the
•most recently received hormone therapy.
•6. Major surgery or radiotherapy within 3 weeks of the first dose of study
•treatment. Patients who received prior radiotherapy to >= 25% of bone marrow are
•not eligible, irrespective of when it was received.
•7. Persistent grade > 1 clinically significant toxicities related to prior
•antineoplastic therapies (except for alopecia); stable sensory neuropathy <=
•grade 1 NCI-CTCAE v. 4.0 is allowed.
•8. History of hypersensitivity reaction or any toxicity attributed to
•trastuzumab, murine proteins or any of the excipients that warranted permanent
•cessation of these agents (applicable for Cohort 1 only).
•9. Previous exposure to vinorelbine (applicable for Cohort 1 triplet
•combination only)
•10. Exposure to the following cumulative anthracycline doses:
•a. Doxorubicin or liposomal doxorubicin > 360 mg/m²
•b. Epirubicin > 720 mg/m²
•c. Mitoxantrone > 120 mg/m² and idarubicin > 90 mg/m²
•d. Other anthracycline at a dose equivalent to > 360 mg/m² doxorubicin
•e. For patients having received > 1 anthracycline, the cumulative dose
•must not exceed the equivalent of 360 mg/m² doxorubicin
•11. Chronic use of high-dose oral corticosteroid therapy (>10 mg of
•prednisone equivalent a day).
•12. Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100
•mmHg) or unstable angina.
•13. History of congestive heart failure of Class II-IV New York Heart
•Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment
•(except atrial fibrillation, paroxysmal supraventricular tachycardia).
•14. History of myocardial infarction within 6 months of study entry.
•15. History of prior or concomitant malignancies (other than excised
•non-melanoma skin cancer or cured in situ cervical carcinoma) within 3 years of
•study entry.
•16. Current dyspnea at rest of any origin, or other diseases requiring
•continuous oxygen therapy.
•17. Current serious illness or medical conditions including, but not limited to
•uncontrolled active infection, clinically significant pulmonary, metabolic or
•psychiatric disorders.
•18. Known HIV, HBV, or HCV infection.
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研究者

发起方

Merus N.V.

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