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

Phase 1

Terminated

• Conditions: EGFR-mutated NSCLC (Disorder)
• Interventions: Combination Product: MP0250 DARPin® drug candidate, Osimertinib

• Registration Number: NCT03418532
• Lead Sponsor: Molecular Partners AG

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-10
• Study First Submitted QC: 2018-01-31
• Study First Posted: 2018-02-01
• Study Start: 2018-03-22
• Primary Completion: 2019-08-30
• Study Completion: 2020-04-24
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-21
• Last Update Posted: 2023-03-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm	MP0250 DARPin® drug candidate, Osimertinib	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

Primary Outcome Measures

Name	Time	Method
Estimate the objective response rate (ORR)	6 months	Tumor response will be assessed based on RECIST 1.1 by using CT or MRI

Secondary Outcome Measures

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

Trial Locations

Locations (10)

Florida Hospital; 🇺🇸 Orlando, Florida, United States

University of California; 🇺🇸 San Diego, California, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

City of Hope - Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

UCLA Medical Center; 🇺🇸 Santa Monica, California, United States

Scottsdale Healthcare Hospitals; 🇺🇸 Scottsdale, Arizona, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Oncology Consultants; 🇺🇸 Houston, Texas, United States

Duke Cancer Institute; 🇺🇸 Durham, North Carolina, United States