Clinical Trials /

MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer

NCT03321981

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: MCLA-128-CL02
  • SECONDARY ID: 2017-002821-39
  • NCT ID: NCT03321981

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
MCLA-128bispecificCohort 1 doublet
TrastuzumabHerceptinCohort 1 doublet
VinorelbineNavelbine, vinorelbine tartrateCohort 1 triplet
Endocrine therapyfulvestrant, exemestane, letrozole, anastrazoleCohort 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 doubletExperimentaltwo step evaluation with safety review after 4-6 patients receiving combination of MCLA-128, 750mg 2hour intravenous infusion in combination with trastuzumab, 8mg/kg first cycle, 6mg/kg other cycles, 90minute intravenous infusion; once per cycle of 21 days.
  • MCLA-128
  • Trastuzumab
Cohort 1 tripletExperimentaltwo step evaluation with safety review after 4-6 patients receiving combination of MCLA-128, 750mg 2hour intravenous infusion once per cycle of 21 days in combination with trastuzumab, 8mg/kg 90minute first cycle, 6mg/kg other cycles, intravenous infusion once per cycle of 21 days and vinorelbine, 25 mg/M2 10minute intravenous infusion twice per cycle of 21 days;
  • MCLA-128
  • Trastuzumab
  • Vinorelbine
Cohort 2ExperimentalMCLA-128, 750mg 2hour intravenous infusion once per cycle of 21 days in combination with same dose and regimen of endocrine therapy prior to study entry and on which the patient progressed.
  • MCLA-128
  • Endocrine therapy

Eligibility Criteria

        Inclusion Criteria:

          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.

          3. Measurable disease as defined by RECIST version 1.1 by radiologic methods on or after
             the most recent line of therapy. For Cohort 2, imaging must be available for central
             review.

          4. Eastern Cooperative Oncology Group performance status of 0 or 1.

          5. Life expectancy of ≥ 12 weeks, as per investigator.

          6. Left ventricular ejection fraction ≥ 50% by echocardiogram or multiple gated
             acquisition scan.

          7. Patients must have adequate organ function

        Exclusion Criteria:

          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.

          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 prior ≥ grade 3 hypersensitivity reaction or any toxicity attributed to
             trastuzumab or murine proteins 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. Chronic use of high-dose oral corticosteroid therapy .

         11. Uncontrolled hypertension or unstable angina.

         12. 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).

         13. History of myocardial infarction within 6 months of study entry.

         14. 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.

         15. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen
             therapy.

         16. Current serious illness or medical conditions including, but not limited to
             uncontrolled active infection, clinically significant pulmonary, metabolic or
             psychiatric disorders.

         17. Known HIV, HBV, or HCV infection.

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

Primary Outcome Measures

Measure:Clinical Benefit Rate at 24 weeks
Time Frame:24 weeks
Safety Issue:
Description: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

Measure:Progression Free Survival (PFS)
Time Frame:Baseline, every 6 weeks until progression up to one year after last patient first treatment
Safety Issue:
Description:the time from treatment start until radiologic progression or death due to any cause
Measure:Overall Response Rate (ORR)
Time Frame:Baseline, every 6 weeks until progression up to one year after last patient first treatment
Safety Issue:
Description:the proportion of patients with overall response of Complete Response or Partial Response based upon RECIST 1.1
Measure:Duration of Response (DoR)
Time Frame:Baseline, every 6 weeks until progression up to one year after last patient first treatment
Safety Issue:
Description:the time from response (Complete Response or Partial Response) until progression or death due to underlying cancer based upon RECIST 1.1
Measure:Overall Survival (OS)
Time Frame:Every 3 months after last visit up to 1 year after last patient first treatment
Safety Issue:
Description:the time from treatment start until death due to any cause
Measure:number of participants with treatment emergent Adverse Events (AE)
Time Frame:continuous until 1 year after last patient last treatment
Safety Issue:
Description:Evaluation of number of participants with Adverse Events
Measure:number of patients that discontinue due to intolerability of study drug
Time Frame:continuous through study completion, an average of 6 months
Safety Issue:
Description:discontinuations due to AEs, dose modifications due to AEs and immunogenicity assessments
Measure:maximum plasma concentration [Cmax]
Time Frame:baseline and 3-12 weeks until last patient last treatment
Safety Issue:
Description:maximum plasma concentration [Cmax] for MCLA-128 as measured from all individual plasma concentration
Measure:trough plasma concentration [C0h]
Time Frame:baseline and 3-12 weeks until last patient last treatment
Safety Issue:
Description:plasma concentration of MCLA-128 as measured at trough level t=0h
Measure:area under curve [AUC]
Time Frame:baseline and 3-12 weeks until last patient last treatment
Safety Issue:
Description:area under the concentration curve [AUC] for MCLA-128
Measure:clearance [CL]
Time Frame:6 weeks
Safety Issue:
Description:clearance [CL] of MCLA-128
Measure:volume of distribution at steady state [Vss]
Time Frame:6 weeks
Safety Issue:
Description:volume of distribution at steady state [Vss] of MCLA-128
Measure:time to reach maximum concentration [tmax]
Time Frame:6 weeks
Safety Issue:
Description:time to reach maximum concentration [tmax] for MCLA-128
Measure:half life [t1/2]
Time Frame:6 weeks
Safety Issue:
Description:half life [t1/2] of MCLA-128
Measure:concentration of trastuzumab at end of infusion [C EOI]
Time Frame:6 weeks
Safety Issue:
Description:concentration of trastuzumab at end of infusion [C EOI]
Measure:trough plasma concentration [C0h] trastuzumab
Time Frame:6 weeks
Safety Issue:
Description:plasma concentration of trastuzumab as measured at trough level t=0h
Measure:anti-drug antibodies serum titers
Time Frame:baseline and 6-12 weeks until last patient last treatment
Safety Issue:
Description:serum titers of anti-drug antibodies against MCLA-128

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Merus N.V.

Trial Keywords

  • Bispecific Antibody IgG1, HER2 HER3
  • MCLA-128
  • Antibodies, bispecific
  • Immunologic Factors
  • Cytokines
  • combination Trastuzumab with and without Vinorelbine

Last Updated

October 23, 2017