| Eligibility |
INCLUSION CRITERIA
1. Have signed and dated written informed consent prior to performing any study
procedure, including screening
2. Are = 18 years old on the day of signing informed consent
3. Have histologically confirmed and documented HER2 positive solid tumor malignancy that
is unresectable, locally advanced, or metastatic with progression
- Part A of study: Assessed on tumor tissue from most recent biopsy
- Part B of study: Assessed on the latest tumor biopsy material for HER2 and other
scheduled tissue testing from within 6 months before entry into the study Part A
and B: Tumor tissue must be made available to the Sponsor for central testing
4. Have received standard, available therapies approved for their cancer, unless they are
unsuitable for these treatments (incurable disease)
- Have documented PD on most recent systemic antitumor treatment
- Disease assessment Part A: Evaluable Disease (disease that cannot be measured
directly by the size of the tumor but can be evaluated by other methods) or
Measurable Disease according to RECIST v1.1 (in case of skin lesions,
documentation by color photography including a ruler to estimate the size of the
lesion is acceptable) Part B: Measurable Disease as per RECIST 1.1
5. Have an ECOG PS of 0-2
6. Have adequate hematological function prior to first scheduled dose, defined as:
- Absolute neutrophil count = 1500 cells/µL
- Hemoglobin = 9 g/dL
- Platelet count = 75,000/µL
- Prothrombin time or activated partial thromboplastin (aPTT) time = 1.5 × upper
limit of normal (ULN)
7. Adequate renal function prior to first scheduled dose, defined as either:
- Serum creatinine = 1.5 mg/dL Or
- Serum creatinine clearance = 40 mL/min (by Cockcroft-Gault equation)
8. Values for potassium, calcium and magnesium must be within normal ranges. Patients may
receive supplements to meet these requirements
9. Adequate hepatic function
- Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) = 2.5 × ULN, or
if known hepatic metastases =5 × ULN
- Total bilirubin = 1.5 × ULN
10. Serum albumin concentration = 30 g/L
11. Highly effective contraception, for both women and men, is ensured:
- Female patients must be either post-menopausal women, or highly effective
contraceptive measures must be ensured. Menopause is defined as occurring 12
months after last menstrual period
- Pre-menopausal or menopausal women who fulfill the following conditions: They
must have had a prior hysterectomy or be using 2 highly effective methods of
contraception (i.e. with failure rates less than 1% per year when used
consistently and correctly, e.g. established use of oral, injected or implanted
hormonal methods of contraception; intrauterine device; condom with spermicidal
foam or gel or film or cream or suppository), from the time of screening through
the whole treatment phase of the study, and for at least 3 months following the
completion of the last MP0274 administration
- Men capable of fathering a child must agree to use barrier contraception
(combination of a condom and spermicide) or limit activity to post-menopausal,
surgically sterilized, or a contraception-practicing partner, during the
treatment phase of the study and for at least 3 months following the completion
of the last MP0274 infusion
- Men capable of fathering a child must refrain from donating sperm for duration of
study and for at least 4 months after last administration of MP0274
12. Female patients of child-bearing potential must have a negative serum pregnancy test
result at screening
EXCLUSION CRITERIA
Patients will be ineligible if 1 or more of the following statements are applicable:
1. Hematological malignancies or other second primary malignancy, that is currently
clinically significant or requires active intervention
2. Known brain metastases that are clinically unstable despite treatment with
anticonvulsives and/or corticosteroids for at least 8 weeks prior to first scheduled
dose of MP0274
3. Receipt of any of the following previous anti-tumor treatments:
- Cumulative doxorubicin = 360 mg/m2
- Cumulative epirubicin = 720 mg/m2
- Lapatinib within 7 days of scheduled dosing Day 1
- Chemotherapy, trastuzumab, or trastuzumab emtansine, other biologics, targeted or
experimental therapy within 4 weeks of scheduled dosing Day 1, and for pertuzumab
within 12 weeks
- Nitrosoureas or mitomycin C chemotherapy within 6 weeks of scheduled dosing Day 1
- Hormonal (e.g. tamoxifen) or aromatase inhibitor therapy within 8 weeks prior to
first dose MP0274, except if no change in dose or schedule 8 weeks prior to first
scheduled dose MP0274
- Newly initiated therapy with bisphosphonate or receptor activator of nuclear
kappa-B ligand (RANKL)-therapy within 8 weeks prior to first scheduled dose
MP0274. If stable on dosing schedule for more than 8 weeks prior to first
scheduled dose MP0274 these therapies are allowed. However, no new therapy with
bisphosphonate/RANKL is allowed during the course of the study
4. Received concurrent radiation therapy within 4 weeks prior to first scheduled dose
MP0274. Local radiation therapy to painful bone metastases following institutional
standard practice for palliative radiotherapy to bone metastases is allowed
5. Presence of neuropathy as residual toxicity after prior anti-tumor therapy Grade > 2
6. Any of the following cardiac exclusion criteria:
- Known history of symptomatic congestive heart failure
- LVEF < 55%, assessed by 2-dimensional echocardiography (2D Echo)
- Known absolute decrease in LVEF of = 15 absolute percentage points on prior
anti-HER2 therapy, even if asymptomatic
- High-risk uncontrolled arrhythmias such as resting bradycardia with a heart rate
< 55 beat/min, atrial tachycardia with a resting heart rate > 100 beats/min,
clinically significant ventricular arrhythmia (ventricular tachycardia) or
higher-grade atrioventricular (AV) block (second degree AV-block Type 2 or third
degree AV-block), implantable pacemaker or defibrillator, family history of long
QT syndrome
- QTc prolongation > Grade 1 (> 480 ms) at screening measured on 2 separate ECGs at
least 10 min apart
- Angina pectoris requiring anti-angina medication
- History of cardiac infarction or evidence of transmural infarction on ECG
- Troponin = Grade 1 (above the upper limit of normal)
- Both, CK > 2.5-fold ULN range and CK-MB > 6% of total CK at screening
- Coronary artery bypass graft, coronary artery angioplasty or stent placement
within 12 months before screening
- Clinically significant valvular heart disease
7. Known hyperthyroidism
8. Hypertension which is not controlled to systolic < 160 mm Hg and diastolic < 100 mm Hg
9. Clinically significant lung disorders such as:
- Non-malignant interstitial lung disease or pneumonitis
- Dyspnea of any cause requiring supplemental oxygen therapy and dyspnea at rest
due to complications of advanced malignancy and co-morbidities
10. History of allogeneic bone marrow or stem cell transplant
11. Known positivity for human immunodeficiency virus (HIV) or history of HIV
12. Patients having active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen [HbsAg] test at screening) or active hepatitis C at
screening
o Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as the presence of hepatitis B core antibody [HbcAb] and absence of HbsAg)
are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only
if polymerase chain reaction is negative for HCV RNA
13. Any active infection requiring the use of parenteral anti-microbial agents or that is
> Grade 2
14. Unable or unwilling to comply with all study requirements for clinical visits,
examinations, tests, and procedures
15. Concurrent participation in another clinical study involving treatment with the IMP
and/or safety follow-up post treatment with IMP (Long-term Survival Follow-up is
permitted)
16. Previous treatment with MP0274 (to exclude re-entering the study)
17. Hypersensitivity to any of the excipients of the finished drug MP0274
18. Patients who are pregnant or breast-feeding
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