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

Conditions:Breast Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:January 15, 2018
End Date:March 30, 2020
Contact:Ernesto Wasserman, MD

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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

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

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.

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

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

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

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

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.
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