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A Phase 1, open-label, multicenter clinical trial of
S095035 (MAT2A inhibitor) in adult participants with
advanced or metastatic solid tumors with homozygous
deletion of MTAP (S095035 in adult participants with advanced or metastatic
solid tumors with deletion of MTAP)

A study of S095035 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

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).
The trial will begin with a dose escalation starting at 50 mg. The DLT evaluation period will be 28 days
(Cycle 1).

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

Administration, Oral

C483889

D000284

Dose-limiting toxicities(DLTs) associated with S095035 administration during the first cycle of treatment
Adverse events(AEs) and serious adverse events, changes in safety laboratory results, changes in the physical examination, vital signs, electrocardiogram(ECG), and Eastern Cooperative Oncology Group(ECOG) performance status(PS)

The following plasma PK parameters (but not limited to): Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t), AUC from time zero to infinity, AUC over one dosing interval at steady state (AUCtau,ss), time to reach maximum concentration (Tmax), maximum concentration (Cmax), trough concentration (Ctrough), half-life (t half), apparent volume of distribution (Vd/F), and apparent clearance (CL/F) (if data is available).

Changes from baseline in plasma concentrations of S-adenosylmethionine (SAM) and other PD biomarker candidates during treatment.

New guidelines for evaluating the therapeutic effect of solid tumors (RECIST version 1.1) and investigator assessment:

Objective response rate (ORR)
Clinical benefit rate (CBR) (CBR = Complete Response [CR] + Partial Response [PR] + Stable Disease [SD] for 6 months or more)
Duration of response (DoR)
Time to response (TTR)

+81-3-3520-0111

No

US/Australia