Clinical Trials /

MP0250 DARPin® Protein Plus Osimertinib in Patients With EGFR-mutated NSCLC

NCT03418532

Description:

The purpose of this study is to assess the anti-tumor efficacy, safety, tolerability, pharmacokinetics (PK), immunogenicity and biological activity of the MP0250 DARPin® drug candidate in combination with osimertinib orally once daily (o.d.), when administered to patients with EGFR mutated, advanced, non squamous NSCLC after tumor progression on osimertinib and on or after the most recent therapy. MP0250 is a multi-DARPin® protein with three specificities, able to simultaneously neutralize the activities of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and also to bind to human serum albumin (HSA) to give an increased plasma half-life and potentially enhanced tumor penetration.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MP0250 DARPin® Protein Plus Osimertinib in Patients With EGFR-mutated NSCLC
  • Official Title: A Phase 1b/2, Single-arm, Open-label, Multi-center Study of MP0250 in Combination With Osimertinib in Patients With EGFR-mutated Non-squamous Non-small Cell Lung Cancer (NSCLC) Pretreated With Osimertinib

Clinical Trial IDs

  • ORG STUDY ID: MP0250-CP202
  • NCT ID: NCT03418532

Conditions

  • EGFR-mutated NSCLC (Disorder)

Purpose

The purpose of this study is to assess the anti-tumor efficacy, safety, tolerability, pharmacokinetics (PK), immunogenicity and biological activity of the MP0250 DARPin® drug candidate in combination with osimertinib orally once daily (o.d.), when administered to patients with EGFR mutated, advanced, non squamous NSCLC after tumor progression on osimertinib and on or after the most recent therapy. MP0250 is a multi-DARPin® protein with three specificities, able to simultaneously neutralize the activities of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and also to bind to human serum albumin (HSA) to give an increased plasma half-life and potentially enhanced tumor penetration.

Trial Arms

NameTypeDescriptionInterventions
single armExperimentalMP0250 DARPin® drug candidate (6 mg/kg or 8 mg/kg or 12 mg/kg, infusion) on day 1 of each 21 day cycle. Osimertinib according to label

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Histologically confirmed metastatic or unresectable locally advanced non-squamous
                 NSCLC with documented EGFR mutation-positive disease
    
              2. Radiologically documented disease progression on previous osimertinib treatment.
    
              3. Radiologically documented disease progression on or after most recent antitumor
                 therapy.
    
              4. Measurable disease according to RECIST 1.1.
    
              5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 2.
    
              6. Men and women ≥18 years old on the day of signing informed consent.
    
              7. Adequate hematological, hepatic and renal function prior to first dose
    
              8. Serum albumin concentration ≥30 g/L
    
              9. Potassium and magnesium within normal range
    
            Exclusion Criteria:
    
              1. Necrotic tumors or tumors close to large blood vessels that may impose an increased
                 bleeding risk when treated with anti-VEGF agents.
    
              2. Second malignancy that is currently clinically significant or required active
                 intervention during the period of 12 months prior to Screening, except early stage
                 non-melanoma skin cancer treated with curative intent.
    
              3. Known pre-existing interstitial or inflammatory lung disease.
    
              4. Clinical signs of or documented leptomeningeal carcinomatosis. Features such as
                 headache, nuchal rigidity, and photophobia may indicate meningeal involvement.
    
              5. Known brain metastases who are clinically unstable
    
              6. Prohibited anti-NSCLC therapies and not having recovered from related AEs to Common
                 Terminology Criteria for Adverse Events (CTCAE) Grade ≤1
    
              7. Any investigational drug within 28 days prior to study treatment.
    
              8. Current participation in any other interventional clinical study (except survival
                 follow up).
    
              9. Neuropathy as residual toxicity after prior antitumor therapy Grade >2
    
             10. Patients taking medications that have the potential to prolong the QT interval
    
             11. Significant cardiac abnormalities
    
             12. Uncontrolled hypertension
    
             13. Significant risk for bleeding
    
             14. Active or recent thrombolic events
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Estimate the objective response rate (ORR)
    Time Frame:6 months
    Safety Issue:
    Description:Tumor response will be assessed based on RECIST 1.1 by using CT or MRI

    Secondary Outcome Measures

    Measure:Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to CTCAE, v4.03.
    Time Frame:15 months
    Safety Issue:
    Description:number of patients with AE/SAE on the base of CTCAE (version 4.03)
    Measure:progression free survival (PFS)
    Time Frame:12 months
    Safety Issue:
    Description:PFS according to RECIST 1.1
    Measure:duration of response (DOR)
    Time Frame:9 months
    Safety Issue:
    Description:DOR according to RECIST 1.1
    Measure:overall survival (OS)
    Time Frame:24 months
    Safety Issue:
    Description:time from the date of first dose of MP0250 until death from any cause or until 1 year for all patients
    Measure:time to response (TTR)
    Time Frame:4 months
    Safety Issue:
    Description:TTR according to RECIST 1.1
    Measure:Incidence of anti-drug (MP0250) antibody formation
    Time Frame:15 months
    Safety Issue:
    Description:determined as titer of anti-drug antibodies
    Measure:pharmacokinetics
    Time Frame:15 months
    Safety Issue:
    Description:half-life
    Measure:pharmacokinetics
    Time Frame:15 months
    Safety Issue:
    Description:clearance
    Measure:pharmacokinetics
    Time Frame:15 months
    Safety Issue:
    Description:AUC
    Measure:pharmacokinetics
    Time Frame:15 months
    Safety Issue:
    Description:Cmax

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Molecular Partners AG

    Trial Keywords

    • DARPin®protein
    • MP0250
    • VEGF
    • HGF
    • NSCLC
    • EGFR mutated
    • Osimertinib

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