Last Update: Feb 26, 2024
An Open-label, Phase I, Dose Escalation, Expansion Study of MGY825 in Adult Patients With Advanced Non-small Cell Lung Cancer
ClinicalTrials.gov Identifier:
Novartis Reference Number:CMGY825A12101
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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

Non-small Cell Lung Cancer
Phase1
Recruiting
140
Oct 05, 2022
Aug 17, 2026
All
18 Years - (Adult, Older Adult)

Interventions

Drug

MGY825

investigational drug

Eligibility 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.

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