Testing MGY825 in patients with advanced non-small cell lung cancer

An Open-label, Phase I, Dose Escalation, Expansion Study of MGY825 in Adult Patients With Advanced Non-small Cell Lung Cancer

This study is testing a new drug called MGY825 to see if it is safe and effective for adults with advanced non-small cell lung cancer that has certain genetic mutations.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Novartis (industry)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 15 sites (Boston, Massachusetts and 14 other locations)
• Trial ID: NCT05275868 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, phase I, multicenter, open-label study evaluating the safety and tolerability of MGY825, a single agent, in adult patients with advanced non-small cell lung cancer (NSCLC). The study includes a dose escalation phase to determine the appropriate dosage and a dose expansion phase to assess preliminary anti-tumor activity. Patients will be enrolled based on their NFE2L2, KEAP1, or CUL3 mutation status, with an exploratory assessment on the effect of food during the dose escalation. The study aims to provide insights into the treatment of advanced NSCLC with specific genetic mutations.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced non-small cell lung cancer who have progressed after prior chemotherapy and PD-(L)1 therapy, especially those with NFE2L2, KEAP1, or CUL3 mutations.

Not a fit: Patients with early-stage non-small cell lung cancer or those who have not received prior platinum-based chemotherapy and PD-(L)1 therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new treatment option for patients with advanced non-small cell lung cancer, particularly those with specific genetic mutations.

How similar studies have performed: Other studies targeting specific mutations in non-small cell lung cancer have shown promise, indicating that this approach may be beneficial.

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.

Where this trial is running

Boston, Massachusetts and 14 other locations

• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• Wash U School of Medicine — Saint Louis, Missouri, United States (ACTIVE_NOT_RECRUITING)
• NYU School of Medicine — New York, New York, United States (RECRUITING)
• Memorial Sloan Kettering Onc. Dept — New York, New York, United States (RECRUITING)
• Uni Of TX MD Anderson Cancer Cntr — Houston, Texas, United States (RECRUITING)
• Novartis Investigative Site — Frankfurt am Main, Hessen, Germany (RECRUITING)
• Novartis Investigative Site — Essen, Germany (RECRUITING)
• Novartis Investigative Site — Koeln, Germany (COMPLETED)
• Novartis Investigative Site — Chuo ku, Tokyo, Japan (RECRUITING)
• Novartis Investigative Site — Seoul, Korea, Republic of (RECRUITING)
• Novartis Investigative Site — Barcelona, Catalunya, Spain (RECRUITING)
• Novartis Investigative Site — Madrid, Spain (RECRUITING)
• Novartis Investigative Site — Geneve 14, Switzerland (RECRUITING)
• Novartis Investigative Site — St Gallen, Switzerland (RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Non-small Cell Lung Cancer, non-small cell lung cancer, NFE2L2, NRF2, KEAP1, CUL3, MGY825