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A Phase 1/2, open-label, multicenter clinical trial investigating the safety, tolerability, pharmacokinetics, and antineoplastic activity of S095035 (MAT2A inhibitor) as a single agent and in combination in adult participants with advanced or metastatic solid tumors with homozygous deletion of MTAP (S095035 as a single agent and in combination in adult participants with advanced or metastatic solid tumors with deletion of MTAP)

A study of S095035 as a single agent and in combination in adult participants with advanced or metastatic solid tumors with deletion of MTAP (CL1-95035-001)

Cooper Michael

Institut de Recherches Internationales Servier (I.R.I.S.)

22 route 128 / rue Francis Perrin 91190 Gif-sur-Yvette, FRANCE

Michael.COOPER@servier.com

International center for therapeutic research clinical operation department

Nihon Servier Company Limited

Otemachi Financial City Grand Cube, 1-9-2 Otemachi, Chiyoda-ku,Tokyo 100-0004, Japan

+81-3-4520-2350

clinicaltrials.jpn@servier.com

Not Recruiting

Jan. 15, 2025

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Males aged 18 years or older, or non-pregnant and non-lactating females.
ECOG PS: 0-1.
Patients with histologically confirmed advanced/metastatic solid tumors who have shown progression after prior treatment regimens and are considered unsuitable for standard therapies.
Participants with pre-existing documented MTAP homozygous deletion in their tumor tissue
Patients able to provide newly obtained tumor biopsy samples before Cycle1Day1 and during treatment.
Patients with adequate hematologic, renal, and hepatic function based on assessments within 7 days prior to the first dose of the investigational drug.

Patients unable to take oral medication or with medical conditions or surgical history that may affect drug absorption.
Patients participating in another interventional study or within less than 5 half-lives of another investigational drug. (Participation in non-interventional registries or epidemiological studies is allowed.)
Patients with active secondary cancer (except for specific non-invasive cancers).
Patients who have undergone major surgery within 4 weeks prior to the first dose of the investigational drug or have not recovered from the side effects of surgery.
Patients with severe or uncontrolled active acute or chronic infections.
Patients with active brain metastases (symptomatic brain metastases or leptomeningeal disease).
Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of S095035.
Patients with medical conditions that exacerbate clinically significant photosensitivity (e.g., solar urticaria, lupus erythematosus).

Both

advanced or metastatic solid tumors with homozygous deletion of MTAP

S095035 (an oral methionine adenosyltransferase 2A [MAT2A] inhibitor) administered orally (PO) once daily (QD) or twice a daily (BID).
The trial will begin with a dose escalation starting at 50 mg. The DLT evaluation period will be 28 days
(Cycle 1).
Japanese study sites will particpate S095035 mono therapy arm, but will not participate S095035 - other drug combination therapy arm.

2-(4-amino-5H-pyrrolo-(3,2-d)pyrimidin-7-yl)-5-methylsulfanylmethylpyrrolidin-3,4-diol [Supplementary Concept]

Administration, Oral

C483889

D000284

Dose escalation part: DLTs associated with S095035 administration during the first cycle of treatment AEs and serious adverse events, changes in safety laboratory results, changes in the physical examination, vital signs, ECG, and ECOG performance status
Dose expansion part: Per RECIST version 1.1 or RANO 2.0 criteria for participants with IDH wild type glioblastoma, as assessed by investigator and by BICR: Objective response rate.

Dose escalation part:
- Plasma PK parameters of S095035
- Changes from baseline in plasma concentrations of SAM and or SDMA residues during treatment.
- Per RECIST version 1.1 or RANO 2.0 criteria for participants with IDH wild type glioblastoma: ORR, BOR, CBR, DOR, TTR

Dose expantion part:
- Per RECIST version 1.1 or RANO 2.0 criteria for participants with IDHwt glioblastoma
BOR, CBR, DOR, TTR, PFS, OS
- Plasma PK parameters of S095035
-incidence and severity of AEs and SAEs, changes in safety laboratory results, changes in the physical examination, vital signs, ECG, and ECOG performance status. Frequency of dose interruptions, dose reductions, and measurements of dose intensity.

+81-3-3520-0111

No

US/Australia/France/Germany/Italy/Spain/Denmark/China