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

This is an interventional treatment trial for Breast Cancer Metastatic focused on measuring Bispecific Antibody IgG1, HER2 HER3, MCLA-128, Antibodies, bispecific, Immunologic Factors, Cytokines, combination Trastuzumab with and without Vinorelbine Read More

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.