Study of MGY825 in Patients With Advanced Non-small Cell Lung Cancer

NCT ID: NCT05275868

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-05

Study Completion Date

2025-10-13

Brief Summary

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Study of MGY825 single agent in adult patients with advanced non-small cell lung cancer.

Detailed Description

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First in human, phase I, multicenter, open-label study of MGY825 single agent with a dose escalation and a dose expansion in adult patients with advanced non-small cell lung cancer (NSCLC).

The dose escalation part investigated the safety and tolerability of MGY825 in adult patients with advanced NSCLC harboring NFE2L2, or KEAP1 or CUL3 (NFE2L2/KEAP1/CUL3) mutations. Patient enrollment was based on locally available test results of mutation status.

An exploratory assessment on the effect of food could be investigated during the dose escalation part.

The dose expansion part assessed the preliminary anti-tumor activity and further assess the safety and tolerability of MGY825 in adult patients with advanced NSCLC divided in two patient groups.

Group 1: Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status.

Group 2: Patients with advanced NSCLC irrespective of prior knowledge of NFE2L2/KEAP1/CUL3 mutational status.

Conditions

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Non-small Cell Lung Cancer

Keywords

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non-small cell lung cancer (NSCLC) NFE2L2 NRF2 KEAP1 CUL3 MGY825

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation

Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status

Group Type EXPERIMENTAL

MGY825

Intervention Type DRUG

investigational drug

Dose expansion group 1

Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status

Group Type EXPERIMENTAL

MGY825

Intervention Type DRUG

investigational drug

Dose expansion group 2

Patients with advanced NSCLC irrespective of prior knowledge of NFE2L2/KEAP1/CUL3 mutational status.

Group Type EXPERIMENTAL

MGY825

Intervention Type DRUG

investigational drug

Interventions

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MGY825

investigational drug

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Signed informed consent must be obtained prior to participation in the study.
* Dose escalation and dose expansion group 1:

Patients with histologically or cytologically confirmed diagnosis of advanced (metastatic or unresectable) NFE2L2/KEAP1/CUL3 mutant NSCLC. Local data confirming the NFE2L2/KEAP1/CUL3 mutation status in tissue must be available for enrollment.

* Dose expansion group 2:

Patients with histologically or cytologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC irrespective of NFE2L2/KEAP1/CUL3 mutation status.

* All patients:

Patients must have progressed after 1 platinum-based chemotherapy regimen and PD-(L)1 antibody therapy either sequentially or concurrent with chemotherapy, where indicated, for Stage IV NSCLC.

Patients treated with neo-adjuvant / adjuvant platinum-based therapy that progressed within 6 months of treatment are permitted to participate.

Prior therapy with VEGF/VEGFR targeting agents is permitted. Prior treatment with approved targeted drugs (e.g., EGFRi, ALKi, METi) is mandatory in patients with NSCLC whose tumor bears actionable mutations.

* Presence of at least one measurable lesion according to RECIST v1.1.
* Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening and during study treatment. A recent biopsy collected after the last systemic treatment and within 3 months before study entry may be submitted at screening.

Exclusion Criteria

* Having out of range laboratory values defined as:

Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) \< 60 mL/min Total bilirubin \> 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN ALT \> 3 x ULN AST \> 3 x ULN ANC \< 1.0 x 109/L Platelet count \< 75 x 109/L Hemoglobin \< 9 g/dL

* Impaired cardiac function or clinically significant cardiac disease, including any of the following:

Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥2), uncontrolled hypertension or clinically significant arrhythmia.

QTcF \> 470 msec on screening ECG or congenital long QT syndrome. Acute myocardial infarction or unstable angina pectoris \< 3 months prior to study entry.

* Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study entry) and at a dose of ≤ 10 mg per day prednisone or equivalent for at least 2 weeks before administration of any study treatment.
* Known active COVID-19 infection.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Wash U School of Medicine

St Louis, Missouri, United States

Site Status

NYU School of Medicine

New York, New York, United States

Site Status

Memorial Sloan Kettering Onc. Dept

New York, New York, United States

Site Status

Memorial Sloan Kettering

New York, New York, United States

Site Status

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, United States

Site Status

Novartis Investigative Site

Frankfurt am Main, Hesse, Germany

Site Status

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Geneva, , Switzerland

Site Status

Novartis Investigative Site

Sankt Gallen, , Switzerland

Site Status

Countries

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United States Germany Japan South Korea Spain Switzerland

Other Identifiers

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2023-504350-36-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CMGY825A12101

Identifier Type: -

Identifier Source: org_study_id