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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05275868
Recruitment Status : Recruiting
First Posted : March 11, 2022
Last Update Posted : February 26, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: MGY825 Phase 1

Detailed Description:

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 will investigate the safety and tolerability of MGY825 in adult patients with advanced NSCLC harboring NFE2L2, or KEAP1 or CUL3 (NFE2L2/KEAP1/CUL3) mutations. Patient enrollment will be based on locally available test results of mutation status.

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

The dose expansion part will assess 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Phase I, Dose Escalation, Expansion Study of MGY825 in Adult Patients With Advanced Non-small Cell Lung Cancer
Actual Study Start Date : October 5, 2022
Estimated Primary Completion Date : August 17, 2026
Estimated Study Completion Date : August 17, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose escalation
Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status
 Drug: MGY825
investigational drug
Experimental: Dose expansion group 1
Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status
 Drug: MGY825
investigational drug
Experimental: Dose expansion group 2
Patients with advanced NSCLC irrespective of prior knowledge of NFE2L2/KEAP1/CUL3 mutational status.
 Drug: MGY825
investigational drug


Outcome Measures
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Primary Outcome Measures :
  1. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 28 months ]
    Assessment of safety of study drug as a single agent

  2. Frequency of dose interruptions and reductions [ Time Frame: 28 months ]
    Assessment of tolerability of study drug as a single agent

  3. Dose intensity [ Time Frame: 28 months ]
    Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.

  4. Incidence and nature of dose limiting toxicities (DLTs) during the first 28 days of treatment with the study drug [ Time Frame: 28 days ]
    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.


Secondary Outcome Measures :
  1. Area under the concentration-time curve (AUC) [ Time Frame: 20 months ]
    Pharmacokinetics (PK) parameters will be determined by non-compartmental methods using the PK profile of the study drug.

  2. Peak concentration (Cmax) [ Time Frame: 20 months ]
    Pharmacokinetics (PK) parameters will be determined by non-compartmental methods using the PK profile of the study drug.

  3. Time to reach maximum drug concentrations in systemic circulation (Tmax) [ Time Frame: 20 months ]
    Pharmacokinetics (PK) parameters will be determined by non-compartmental methods using the PK profile of the study drug.

  4. Overall response rate (ORR) per RECIST 1.1 [ Time Frame: 28 months ]
    Evaluation of preliminary anti-tumor activity of study drug as single agent

  5. Progression free survival (PFS) per RECIST 1.1 [ Time Frame: 28 months ]
    Evaluation of preliminary anti-tumor activity of study drug as single agent

  6. Duration of response (DOR) per RECIST 1.1 [ Time Frame: 28 months ]
    Evaluation of preliminary anti-tumor activity of study drug as single agent


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Unable or unwilling to swallow capsules as per dosing schedule. Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05275868


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
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United States, Massachusetts
Massachusetts General Hospital Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Brian Kelter       bkelter@partners.org   
Principal Investigator: Jessica Jiyeong Lin         
Dana Farber Cancer Institute . Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jennifer Luu    617-632-5136    Jennifer_Luu@DFCI.HARVARD.EDU   
Principal Investigator: Mark Awad         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Gina Vellequette       g.vellequette@wustl.edu   
Principal Investigator: Daniel Morgensztern         
United States, New York
NYU School of Medicine NYU School of Med-Langone Recruiting
New York, New York, United States, 10015
Contact: Selena Harrichand       Selena.Harrichand@nyulangone.org   
Principal Investigator: Vamsidhar Velcheti         
Memorial Sloan Kettering Onc. Dept Recruiting
New York, New York, United States, 10017
Contact: Paul Paik    646-608-3759    paikp@mskcc.org   
Principal Investigator: Paul Paik         
United States, Texas
Uni of TX MD Anderson Cancer Cntr Recruiting
Houston, Texas, United States, 77030
Contact    713-792-2921      
Principal Investigator: Ferdinandos Skoulidis         
Germany
Novartis Investigative Site Recruiting
Frankfurt, Germany, 60590
Novartis Investigative Site Recruiting
Koeln, Germany, 50924
Japan
Novartis Investigative Site Recruiting
Chuo ku, Tokyo, Japan, 104 0045
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Switzerland
Novartis Investigative Site Recruiting
Geneve 14, Switzerland, CH 1211
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05275868    
Other Study ID Numbers: CMGY825A12101
2021-006793-22 ( EudraCT Number )
First Posted: March 11, 2022    Key Record Dates
Last Update Posted: February 26, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
non-small cell lung cancer (NSCLC)
NFE2L2
NRF2
 KEAP1
CUL3
MGY825
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms