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

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.