EGFR-mutated NSCLC (Disorder) Clinical Trial
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
| Verified date | March 2023 |
| Source | Molecular Partners AG |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 8 |
| Est. completion date | April 24, 2020 |
| Est. primary completion date | August 30, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | UT Southwestern Medical Center | Dallas | Texas |
| United States | City of Hope - Comprehensive Cancer Center | Duarte | California |
| United States | Duke Cancer Institute | Durham | North Carolina |
| United States | Oncology Consultants | Houston | Texas |
| United States | Tennessee Oncology | Nashville | Tennessee |
| United States | Florida Hospital | Orlando | Florida |
| United States | University of California | San Diego | California |
| United States | UCLA Medical Center | Santa Monica | California |
| United States | Scottsdale Healthcare Hospitals | Scottsdale | Arizona |
| United States | Georgetown University | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Molecular Partners AG |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | biomarkers in tissue | biomarkers associated with response or resistance to MP0250, HGF by IHC | 12 months | |
| Other | biomarkers in blood | biomarkers associated with response or resistance to MP0250, HGF by ELISA | 12 months | |
| Primary | Estimate the objective response rate (ORR) | Tumor response will be assessed based on RECIST 1.1 by using CT or MRI | 6 months | |
| Secondary | 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 | |
| Secondary | progression free survival (PFS) | PFS according to RECIST 1.1 | 12 months | |
| Secondary | duration of response (DOR) | DOR according to RECIST 1.1 | 9 months | |
| Secondary | 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 | |
| Secondary | time to response (TTR) | TTR according to RECIST 1.1 | 4 months | |
| Secondary | Incidence of anti-drug (MP0250) antibody formation | determined as titer of anti-drug antibodies | 15 months | |
| Secondary | pharmacokinetics | half-life | 15 months | |
| Secondary | pharmacokinetics | clearance | 15 months | |
| Secondary | pharmacokinetics | AUC | 15 months | |
| Secondary | pharmacokinetics | Cmax | 15 months |