Trial record 1 of 1 for:
NCT03321981
MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer
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| ClinicalTrials.gov Identifier: NCT03321981 |
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Recruitment Status :
Active, not recruiting
First Posted : October 26, 2017
Last Update Posted : August 11, 2022
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Sponsor:
Merus N.V.
Information provided by (Responsible Party):
Merus N.V.
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Brief Summary:
A Phase 2, open-label, multicenter international study will be performed to evaluate the efficacy of MCLA-128-based combinations. Three combination treatments will be evaluated, two in Cohort 1 and one in Cohort 2.
MCLA-128 is given in combinations in two metastatic breast cancer (MBC) populations, HER2-positive/amplified (Cohort 1) and Estrogen Receptor-positive/low HER2 expression (Cohort2).
Two combinations treatments will be evaluated in Cohort 1, the doublet and triplet. Initially MCLA-128 is given in combination with trastuzumab in the doublet. After the safety of the doublet has been assessed in 4-6 patients, MCLA-128 is given in combination with trastuzumab and vinorelbine in the triplet, in parallel to the efficacy expansion of the doublet.
The doublet and triplet combinations are both evaluated in two steps with an initial safety run-in followed by a cohort efficacy expansion. In total up to 40 patients evaluable for efficacy are included in both the doublet and triplet.
In Cohort 2 MCLA-128 is administered in combination with the same previous endocrine therapy on which progressive disease is radiologically documented. A total of up to 40 patients evaluable for efficacy are included in the Cohort 2.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer Metastatic | Drug: MCLA-128 Drug: Trastuzumab Drug: Vinorelbine Drug: Endocrine therapy | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 101 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | three combination treatments will be evaluated, two in Cohort 1 and one in Cohort 2 |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | January 15, 2018 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | February 15, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
Drug Information available for:
Trastuzumab
| Arm | Intervention/treatment |
|---|---|
| Experimental: Cohort 1 doublet |
Drug: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: bispecific Drug: Trastuzumab humanised IgG1 monoclonal antibody
Other Name: Herceptin |
| Experimental: Cohort 1 triplet |
Drug: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: bispecific Drug: Trastuzumab humanised IgG1 monoclonal antibody
Other Name: Herceptin Drug: Vinorelbine antineoplastic drug of vinca alkaloid family
Other Names:
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| Experimental: Cohort 2 |
Drug: MCLA-128
full length IgG1 bispecific antibody targeting HER2 and HER3
Other Name: bispecific Drug: Endocrine therapy same endocrine therapy is administered as the last line of endocrine therapy
Other Names:
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Primary Outcome Measures :
- Clinical Benefit Rate at 24 weeks [ Time Frame: 24 weeks ]The proportion of patients with a best overall response of Complete Response, Partial Response or Stable Disease at 24 weeks based upon RECIST 1.1
Secondary Outcome Measures :
- Progression Free Survival (PFS) [ Time Frame: Baseline, every 6 weeks until progression up to one year after last patient first treatment ]the time from treatment start until radiologic progression or death due to any cause
- Overall Response Rate (ORR) [ Time Frame: Baseline, every 6 weeks until progression up to one year after last patient first treatment ]the proportion of patients with overall response of Complete Response or Partial Response based upon RECIST 1.1
- Duration of Response (DoR) [ Time Frame: Baseline, every 6 weeks until progression up to one year after last patient first treatment ]the time from response (Complete Response or Partial Response) until progression or death due to underlying cancer based upon RECIST 1.1
- Overall Survival (OS) [ Time Frame: Every 3 months after last visit up to 1 year after last patient first treatment ]the time from treatment start until death due to any cause
- number of participants with treatment emergent Adverse Events (AE) [ Time Frame: continuous until 1 year after last patient last treatment ]Evaluation of number of participants with Adverse Events
- number of patients that discontinue due to intolerability of study drug [ Time Frame: continuous through study completion, an average of 6 months ]discontinuations due to AEs, dose modifications due to AEs and immunogenicity assessments
- maximum plasma concentration [Cmax] [ Time Frame: baseline and 3-12 weeks until last patient last treatment ]maximum plasma concentration [Cmax] for MCLA-128 as measured from all individual plasma concentration
- trough plasma concentration [C0h] [ Time Frame: baseline and 3-12 weeks until last patient last treatment ]plasma concentration of MCLA-128 as measured at trough level t=0h
- area under curve [AUC] [ Time Frame: baseline and 3-12 weeks until last patient last treatment ]area under the concentration curve [AUC] for MCLA-128
- clearance [CL] [ Time Frame: 6 weeks ]clearance [CL] of MCLA-128
- volume of distribution at steady state [Vss] [ Time Frame: 6 weeks ]volume of distribution at steady state [Vss] of MCLA-128
- time to reach maximum concentration [tmax] [ Time Frame: 6 weeks ]time to reach maximum concentration [tmax] for MCLA-128
- half life [t1/2] [ Time Frame: 6 weeks ]half life [t1/2] of MCLA-128
- concentration of trastuzumab at end of infusion [C EOI] [ Time Frame: 6 weeks ]concentration of trastuzumab at end of infusion [C EOI]
- trough plasma concentration [C0h] trastuzumab [ Time Frame: 6 weeks ]plasma concentration of trastuzumab as measured at trough level t=0h
- anti-drug antibodies serum titers [ Time Frame: baseline and 6-12 weeks until last patient last treatment ]serum titers of anti-drug antibodies against MCLA-128
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Signed informed consent before initiation of any study procedures.
- 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.
- Measurable disease as defined by RECIST version 1.1 by radiologic methods on or after the most recent line of therapy. For Cohort 2 patients with bone-only disease are eligible even in absence of measurable disease and must have lytic or mixed lesions. For Cohort 2, imaging must be available for central review.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Life expectancy of ≥ 12 weeks, as per investigator.
- Left ventricular ejection fraction ≥ 50% by echocardiogram or multiple gated acquisition scan.
- Adequate organ function
Exclusion Criteria:
- 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.
- Known leptomeningeal involvement.
- Advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term.
- Participation in another interventional clinical trial or treatment with any investigational drug within 4 weeks prior to study entry.
- Any systemic anticancer therapy within 3 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity a washout period of 6 weeks is required. For patients in Cohort 2, this does not apply to the most recently received hormone therapy.
- 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.
- Persistent grade > 1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 1 NCI-CTCAE v. 4.03 is allowed.
- History of hypersensitivity reaction or any toxicity attributed to trastuzumab or murine proteins that warranted permanent cessation of these agents (applicable for Cohort 1 only).
- Previous exposure to vinorelbine (applicable for Cohort 1 triplet combination only)
- Exposure to specific cumulative anthracycline doses
- Chronic use of high-dose oral corticosteroid therapy .
- Uncontrolled hypertension or unstable angina.
- 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).
- History of myocardial infarction within 6 months of study entry.
- 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.
- Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy.
- Current serious illness or medical conditions including, but not limited to uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders.
- Known HIV, HBV, or HCV infection.
- Pregnant or lactating women; women of childbearing potential must use effective contraception methods prior to study entry, for the duration of study participation, and for 6 months after the last dose of MCLA-128.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03321981
Locations
Show 25 study locations
Sponsors and Collaborators
Merus N.V.
Investigators
| Study Director: | Ernesto Wasserman, MD | Merus N.V. |
| Responsible Party: | Merus N.V. |
| ClinicalTrials.gov Identifier: | NCT03321981 |
| Other Study ID Numbers: |
MCLA-128-CL02 2017-002821-39 ( EudraCT Number ) |
| First Posted: | October 26, 2017 Key Record Dates |
| Last Update Posted: | August 11, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Merus N.V.:
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Bispecific Antibody IgG1, HER2 HER3 MCLA-128 Antibodies, bispecific |
Immunologic Factors Cytokines combination Trastuzumab with and without Vinorelbine |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Trastuzumab Letrozole Vinorelbine Fulvestrant Exemestane Antineoplastic Agents, Immunological Antineoplastic Agents Aromatase Inhibitors |
Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Antineoplastic Agents, Hormonal Estrogen Receptor Antagonists |