Clinical trial NCT03418532: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: EGFR-mutated NSCLC (Disorder)
Keywords: DARPin®protein
MP0250
VEGF
HGF
NSCLC
EGFR mutated
Osimertinib
Lead sponsor: Molecular Partners AG
Sponsor class: INDUSTRY
First posted: 2018-02-01
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The trial was intended to be a Phase 1/2 trial. Trial was terminated before Phase 2 commenced.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Estimate the objective response rate (ORR)
timeFrame: 6 months
Secondary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to CTCAE, v4.03.
timeFrame: 15 months
measure: progression free survival (PFS)
timeFrame: 12 months
measure: duration of response (DOR)
timeFrame: 9 months
measure: overall survival (OS)
timeFrame: 24 months
measure: time to response (TTR)
timeFrame: 4 months
measure: Incidence of anti-drug (MP0250) antibody formation
timeFrame: 15 months
measure: pharmacokinetics
timeFrame: 15 months
measure: pharmacokinetics
timeFrame: 15 months
measure: pharmacokinetics
timeFrame: 15 months
measure: pharmacokinetics
timeFrame: 15 months
Other outcomes:
measure: biomarkers in tissue
timeFrame: 12 months
measure: biomarkers in blood
timeFrame: 12 months
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals
state: Arizona
city: Duarte
country: United States
facility: City of Hope - Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: University of California
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
Study officials:
References: