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

NCT05275868 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CMGY825A121012023-504350-36-00
• Study Type: interventional
• Target: 41
• Locations: 6 countries
• Sites: 15

Brief Summary

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

Conditions

Non-small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Assessment of safety of study drug as a single agent

  28 months

• Frequency of dose interruptions and reductions

  Assessment of tolerability of study drug as a single agent

  28 months

• Dose intensity

  Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.

  28 months

• Incidence and nature of dose limiting toxicities (DLTs) during the first 28 days of treatment with the study drug

  A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 assessed as not primarily related to disease, disease progression, inter-current illness or concomitant medications that occurs during the first 28 days of treatment with the study drug. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

  28 days

Secondary Outcomes (6)

• Area under the concentration-time curve (AUC)

  20 months

• Peak concentration (Cmax)

  20 months

• Time to reach maximum drug concentrations in systemic circulation (Tmax)

  20 months

• Overall response rate (ORR) per RECIST 1.1

  28 months

• Progression free survival (PFS) per RECIST 1.1

  28 months

Study Arms (3)

Dose escalation

EXPERIMENTAL

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

Drug: MGY825

Dose expansion group 1

EXPERIMENTAL

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

Drug: MGY825

Dose expansion group 2

EXPERIMENTAL

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

Drug: MGY825

Interventions

MGY825 DRUG

investigational drug

Dose escalation; Dose expansion group 1; Dose expansion group 2

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Wash U School of Medicine

St Louis, Missouri, 63110, United States

Location

NYU School of Medicine

New York, New York, 10015, United States

Location

Memorial Sloan Kettering Onc. Dept

New York, New York, 10017, United States

Location

Memorial Sloan Kettering

New York, New York, 10017, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Geneva, CH 1211, Switzerland

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 11, 2022
• Study Start: October 5, 2022
• Primary Completion: October 13, 2025
• Study Completion: October 13, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); KR (1); CH (2); DE (3); ES (1); US (7)