Clinical Trials /

First-in-human Study to Investigate Safety, Blood Levels and Activity of MP0274 in Cancer Patients With HER2-positive Solid Tumors

NCT03084926

Description:

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-human Study to Investigate Safety, Blood Levels and Activity of MP0274 in Cancer Patients With HER2-positive Solid Tumors
  • Official Title: A Phase 1, First-in-human, Single-arm, Multi-center, Open-label, Repeated‑Dose, Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of MP0274 in Patients With Advanced HER2-positive Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MP0274-CP101
  • SECONDARY ID: 2016-004712-36
  • NCT ID: NCT03084926

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
MP0274MP0274

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
MP0274Experimental
  • MP0274

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events
Time Frame:from first infusion to end-of-study visit, up to 12 months
Safety Issue:
Description:Number and grading according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Secondary Outcome Measures

Measure:Pharmacokinetics of MP0274
Time Frame:from first infusion to end-of-study visit, up to 12 months
Safety Issue:
Description:Serum concentration-time profile of MP0274
Measure:Preliminary assessment of anti-tumor activity of MP0274
Time Frame:from first infusion to end-of-study visit, up to 12 months
Safety Issue:
Description:Efficacy evaluation based on Response Evaluation Criteria in Solid Tumors (RECIST)
Measure:Incidence of anti-drug-antibodies
Time Frame:from first infusion to end-of-study visit, up to 12 months
Safety Issue:
Description:Serum concentration-time profile of anti-drug antibodies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Molecular Partners AG

Last Updated

October 9, 2017