Phase I study of MGY825 in patients with advanced non-small cell lung cancer

JRCT ID: jRCT2031220278

Registered date:19/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: advanced non-small cell lung cancer
• Date of first enrollment: 05/10/2022
• Target sample size: 12
• Countries of recruitment: Spain,Japan
• Study type: Interventional
• Intervention(s): MGY825

Outcome(s)

Primary Outcome

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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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/or PD-(L)1 antibody therapy, where indicated, for Stage IV NSCLC Prior therapy with VEGF/VEGFR targeting agents is permitted Prior neo-adjuvant / adjuvant therapy 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.

Exclude criteria

Having out of range laboratory values defined as:
Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40 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.

Related Information

• Primary Sponsor: Yamauchi Kyosuke
• Secondary ID(s): NCT05275868