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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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EGFR-mutated NSCLC (Disorder)

Intervention / Treatment
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* Combination Product: MP0250 DARPin® drug candidate, Osimertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or unresectable locally advanced non-squamous NSCLC with documented EGFR mutation-positive disease Radiologically documented disease progression on previous osimertinib treatment. Radiologically documented disease progression on or after most recent antitumor therapy. Measurable disease according to RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 2. Men and women ≥18 years old on the day of signing informed consent. Adequate hematological, hepatic and renal function prior to first dose Serum albumin concentration ≥30 g/L Potassium and magnesium within normal range Exclusion Criteria: Necrotic tumors or tumors close to large blood vessels that may impose an increased bleeding risk when treated with anti-VEGF agents. 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. Known pre-existing interstitial or inflammatory lung disease. Clinical signs of or documented leptomeningeal carcinomatosis. Features such as headache, nuchal rigidity, and photophobia may indicate meningeal involvement. Known brain metastases who are clinically unstable Prohibited anti-NSCLC therapies and not having recovered from related AEs to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤1 Any investigational drug within 28 days prior to study treatment. Current participation in any other interventional clinical study (except survival follow up). Neuropathy as residual toxicity after prior antitumor therapy Grade >2 Patients taking medications that have the potential to prolong the QT interval Significant cardiac abnormalities Uncontrolled hypertension Significant risk for bleeding Active or recent thrombolic events

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The trial was intended to be a Phase 1/2 trial. Trial was terminated before Phase 2 commenced.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br>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 | Combination Product: MP0250 DARPin® drug candidate, Osimertinib<br>* Number of Cycles: until progression, unacceptable toxicity or other reasons for withdrawal<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DARPin®protein, MP0250, VEGF, HGF, NSCLC, EGFR mutated, Osimertinib