Phase I/II, Open Label, Dose Escalating Study To Investigate Safety, Tolerability, And Preliminary Efficacy Of The Trifunctional Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab In Patients With HER-2/Neu Expressing (1+/SISH Positive, 2+ and 3+) Solid Tumors Progressing After Standard Therapy
- Signed and dated informed consent form.
- Male or female patients aged ≥ 18 years and with a life expectancy of at least 4
- Negative pregnancy test at screening (and not more than 72 hours prior to the first
ertumaxomab infusion) for women of childbearing potential. Patients must agree to use
adequate contraception during the study.
- Measurable disease, defined as at least one lesion that is measurable in one
- Solid HER2/neu positive tumors (1+/SISH positive, 2+, and 3+), histologically
- Patients must have disease progression during or after standard therapy and/or are no
longer feasible for approved therapies.
- Previous therapies must be discontinued at least 2 weeks (6 weeks in case mitomycin
C) prior to administration of ertumaxomab and all treatment related toxicities must
have resolved or decreased to common toxicity criteria (CTC) grade 1 (with the
exception of alopecia and peripheral neuropathy).
- If patients have received HER2-targeting therapies, all HER2-targeting therapies must
have been discontinued before study entry.
- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
- Adequate hematological, liver and kidney function:
- Adequate recovery from prior systemic therapy.
- Patients capable to understand the purposes and risks of the study, and who are
willing and able to participate in the study
- Left ventricular ejection fraction must be > 50% at echocardiography
- Patients currently being treated with medication or anticonvulsants for brain or
central nervous system metastases or patients that have documented radiologic
evidence of active brain or central nervous system metastases within 12 weeks of
- Patients with a prior diagnosis of any other malignancy (unless cured by surgery or
other appropriate treatments greater than 2 years before study entry). Patients with
in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the
skin may be included at any time.
- ≥ 5 preceding chemotherapies
- Documented acute or chronic infection or other concurrent non-malignant co
morbidities that are uncontrolled, such as unstable or uncontrolled pectorial angina,
myocardial infarction during the last 6 months, valvular heart disease that requires
treatment, acute myocarditis or congestive heart failure (CHF, NYHA III or IV).
- Patients with a known human immunodeficiency virus, hepatitis B or hepatitis C
positive status are excluded from participation in the study
- Any concurrent chemotherapy, radiotherapy (except for local radiation therapy for
bone marrow metastasis), hormonal therapy, immunotherapy or corticoid therapy.
- Treatment with any investigational product within 2 weeks prior to first
administration of ertumaxomab.
- Patients with documented autoimmune diseases.
- Known hypersensitivity to murine proteins and any other component of the drug.
- Abnormal organ or bone marrow function as defined below (any single parameter to
- ANC < 1.5 Gpt/l (1.5x109/L, 1500/mm3)
- Hemoglobin <9.0 g/dl
- Platelet count < 75Gpt/l (75x109/L, 75,000/mm³)
- AST(SGOT)/ALT(SGPT) > 3 x upper limit of normal (ULN); or: in case of
metastatic liver disease AST(SGOT)/ALT(SGPT) > 5 x ULN
- Alkaline Phospatase > 2.5 x ULN
- Serum (total) bilirubin > 1,5 x ULN for the institution; or in case of
metastatic liver disease: Serum (total) bilirubin > 3 x ULN for the institution;
- Serum creatinine > 1.5 x ULN
- Any other concurrent disease or medical conditions that are deemed to interfere with
the conduct of the study as judged by the investigator.
- Known hypersensitivity to ertumaxomab and its analogues in general, or to any other
component of the study drug formulation.
- Pregnant women, nursing mothers, lactating women, and women of child-bearing
potential who are unwilling to use effective contraception (see above).
- Use of immune-suppressive agents for the past 4 weeks prior to the first
administration of ertumaxomab. For regular use of systemic corticosteroids, patients
should only be included after stepwise discontinuation to be free of steroids for a
minimum of 7 days prior to first treatment.
- Unwilling or unable to follow protocol requirements.