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.
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
Name | Type | Description | Interventions |
---|
single arm | Experimental | MP0250 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: | Terminated |
Lead Sponsor: | Molecular Partners AG |
Trial Keywords
- DARPin®protein
- MP0250
- VEGF
- HGF
- NSCLC
- EGFR mutated
- Osimertinib
Last Updated
May 29, 2020