This study is investigating a new experimental therapy, MP0274, a DARPin® drug candidate
targeting HER2. Preclinical studies suggest that MP0274 may provide additional benefit for
the treatment of HER2-positive cancers. This is the first study of MP0274 in humans and its
main purpose is to test its safety and tolerability in patients with HER2-positive cancer.
This study will also examine the blood levels of MP0274 at several escalating dose levels and
a recommended dose for further development will be determined. The recommended dose will be
tested in a second part of the study to confirm safety and to further assess the preliminary
biologic and anti-tumor activity
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
4. Have received standard, available therapies approved for their cancer, unless they are
unsuitable for these treatments (incurable disease)
5. Have progressive disease (PD) documented by medical imaging
6. Have measurable disease according to RECIST v1.1
7. Are amenable to computed tomography (CT) or magnetic resonance imaging (MRI)
8. Have an ECOG performance status (PS) of 0-2
9. Have adequate hematological function prior to first dose, defined as:
- ANC ≥ 1500 cells/µL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 75,000/µL
- Prothrombin time or partial thromboplastin time ≤ 1.5 x upper limit of normal
(ULN)
10. Adequate hepatic function prior to first dose, defined as
- Total bilirubin ≤ 1.5 x ULN (unless Gilbert's syndrome)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤
5 x ULN if known hepatic metastases
11. Adequate renal function prior to first dose, defined as either:
- Serum creatinine ≤1.5 mg/dL
Or:
- Serum creatinine clearance ≥ 40 mL/min (by Cockcroft-Gault equation)
12. Serum albumin concentration ≥ 30 g/L
13. Blood vessels accessible for intravenous infusion
14. Highly effective contraception, for both women and men, is ensured
15. Female patients of child-bearing potential must have a negative serum pregnancy test
result at screening and a negative urine pregnancy test at baseline
16. Able to communicate well with the Investigator, and to understand and comply with the
requirements of the study
Exclusion Criteria:
1. Hematological malignancies or other second primary malignancy, that is currently
clinically significant or requires active intervention
2. Known brain metastases who are clinically unstable despite treatment with
anticonvulsives and/or corticosteroids for at least 8 weeks prior to study entry
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, pertuzumab, or trastuzumab emtansine, other biologics,
targeted or experimental therapy within 4 weeks of scheduled dosing Day 1
- 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
study entry, except if no change in dose or schedule within 8 weeks prior to
study entry
- Newly initiated therapy with bisphosphonate or receptor activator of nuclear
kappa-B ligand (RANKL)-therapy within 8 weeks prior to screening. If stable on
dosing schedule for more than 8 weeks prior study entry 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 screening. Local low
dose radiation to bone lesions for local pain control is allowed in the absence of PD
per RECIST v1.1
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) or multi-gated
acquisition (MUGA) scan
- Known absolute decrease in LVEF of ≥ 15 absolute percentage points on prior
anti-HER2 therapy, even if asymptomatic
- High-risk uncontrolled arrhythmias such as atrial tachycardia with a heart rate >
100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or
higher-grade atrioventricular (AV) block (second degree AV-block Type 2 or third
degree AV-block)
- Angina pectoris requiring anti-angina medication
- Clinically significant valvular heart disease
- History of cardiac infarction or evidence of transmural infarction on ECG
- Coronary artery bypass graft, coronary artery angioplasty or stent placement
within 12 months
7. Hypertension which is not controlled to systolic < 160 mm Hg and diastolic < 100 mm Hg
8. Clinically significant lung disorders such as:
- Non-malignant interstitial lung disease (ILD) or pneumonitis
- Dyspnea of any cause requiring supplemental oxygen therapy and dyspnea at rest
due to complications of advanced malignancy and co-morbidities
9. Prior bone marrow or stem cell transplant
10. Known positivity for human immunodeficiency virus (HIV)
11. Known active hepatitis B (chronic or acute; defined as having a positive hepatitis B
surface antigen [HbsAg] test at screening) or known active hepatitis C
12. Any active infection requiring the use of parenteral anti-microbial agents or that is
> Grade 2
13. Unable or unwilling to comply with all study requirements for clinical visits,
examinations, tests, and procedures
14. Concurrent participation in another clinical trial involving study treatment and/or
safety follow-up post study treatment (survival follow-up is permitted)
15. Previous treatment with MP0274 (to exclude re-entering the study)
16. Hypersensitivity to any of the excipients of the finished drug MP0274
17. Patients who are pregnant or breast-feeding