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

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

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.

Study Overview

• Status: Terminated
• Conditions: EGFR-mutated NSCLC (Disorder)
• Intervention / Treatment: Combination product: MP0250 DARPin® drug candidate, Osimertinib

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Hospitals
  • California
    • Duarte, California, United States, 91010
      • City of Hope - Comprehensive Cancer Center
    • San Diego, California, United States, 92093
      • University of California
    • Santa Monica, California, United States, 90404
      • UCLA Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Oncology Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm; 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; Number of Cycles: until progression, unacceptable toxicity or other reasons for withdrawal

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarkers in tissue	biomarkers associated with response or resistance to MP0250, HGF by IHC	12 months
biomarkers in blood	biomarkers associated with response or resistance to MP0250, HGF by ELISA	12 months

Collaborators and Investigators

• Sponsor: Molecular Partners AG

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): April 24, 2020

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; VEGF; Osimertinib; HGF; DARPin®protein; MP0250; EGFR mutated
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: MP0250-CP202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No