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.
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
Interventions
Drug | Synonyms | Arms |
---|
MCLA-128 | bispecific | Cohort 1 doublet |
Trastuzumab | Herceptin | Cohort 1 doublet |
Vinorelbine | Navelbine, vinorelbine tartrate | Cohort 1 triplet |
Endocrine therapy | fulvestrant, exemestane, letrozole, anastrazole | Cohort 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
Name | Type | Description | Interventions |
---|
Cohort 1 doublet | Experimental | | |
Cohort 1 triplet | Experimental | | - MCLA-128
- Trastuzumab
- Vinorelbine
|
Cohort 2 | Experimental | | - 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 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.
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. 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 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. 4.03
is allowed.
8. 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).
9. Previous exposure to vinorelbine (applicable for Cohort 1 triplet combination only)
10. Exposure to specific cumulative anthracycline doses
11. Chronic use of high-dose oral corticosteroid therapy .
12. Uncontrolled hypertension 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.
19. 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: | Active, not 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
August 26, 2021