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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT05275868

Studienbeginn:
Oktober 2022

Letztes Update:
26.02.2024

Wirkstoff:
MGY825

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations
(3 von 12)

Novartis Investigative Site
60590 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
50924 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
104 0045 Chuo ku
JapanRekrutierend» Google-Maps
Novartis Investigative Site
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Novartis Investigative Site
CH 1211 Geneve 14
SwitzerlandRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

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.

Secondary outcome:

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

Studien-Arme

  • Experimental: Dose escalation
    Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status
  • Experimental: Dose expansion group 1
    Patients with advanced NSCLC harboring NFE2L2/KEAP1/CUL3 mutations enrolled based on locally available test results of mutation status
  • Experimental: Dose expansion group 2
    Patients with advanced NSCLC irrespective of prior knowledge of NFE2L2/KEAP1/CUL3 mutational status.

Geprüfte Regime

  • MGY825:
    investigational drug

Quelle: ClinicalTrials.gov


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