S095035 in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of the Methylthioadenosine Phosphorylase (MTAP) Gene

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ClinicalTrials.gov Identifier: NCT06188702

Recruitment Status : Recruiting

First Posted : January 3, 2024

Last Update Posted : May 2, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

Institut de Recherches Internationales Servier

Information provided by (Responsible Party):

Servier ( Servier Bio-Innovation LLC )

Tracking Information

First Submitted Date ^ICMJE

December 18, 2023

First Posted Date ^ICMJE

January 3, 2024

Last Update Posted Date

May 2, 2024

Actual Study Start Date ^ICMJE

April 29, 2024

Estimated Primary Completion Date

May 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Dose limiting toxicities (DLTs) associated with S095035 administration during the first cycle of treatment [ Time Frame: Through cycle 1 (each cycle is 28 days) ]
Total number of adverse events (AEs) [ Time Frame: Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) ]
Total number of serious adverse events (SAEs) [ Time Frame: Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
AUC from 0 to infinity (AUC0-∞) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
AUC over 1 dosing interval at steady state (AUCtau,ss) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Time to maximum concentration (Tmax) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Maximum concentration (Cmax) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Trough concentration (Ctrough) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Half-life (t½) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Apparent volume of distribution (Vd/F) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Apparent clearance (CL/F) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Change from baseline in plasma concentrations of S-adenosylmethionine (SAM) [ Time Frame: Through the last dose of study treatment (approximately 2 years) ]
Objective response rate [ Time Frame: Through the end of the study (approximately 2 years) ]
Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment
Clinical benefit rate (CBR) [ Time Frame: Through the end of the study (approximately 2 years) ]
CBR=complete response [CR]+partial response [PR]+stable disease [SD] ) ≥6 months, Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment
Duration of response [ Time Frame: Through the end of the study (approximately 2 years) ]
Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment. The time from date of first documented confirmed CR or confirmed PR to date of first documented disease progression or death due to any cause.
Time to response [ Time Frame: Through the end of the study (approximately 2 years) ]
Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment. The time from the date of randomization to date of first documented confirmed complete response (CR) or confirmed partial response (PR).

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

S095035 in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of the Methylthioadenosine Phosphorylase (MTAP) Gene

Official Title ^ICMJE

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

Brief Summary

This is a first-in-human Phase 1, multicenter, open-label dose escalation study of S095035 in adult participants with advanced or metastatic solid tumors with homozygous deletion of MTAP who have failed to respond to or have progressed after at least 1 prior treatment regimen, and for whom additional effective standard treatment is not available. S095035 is an oral methionine adenosyltransferase 2A [MAT2A] inhibitor.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1

Study Design ^ICMJE

Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

MTAP-deleted Solid Tumors

Intervention ^ICMJE

Drug: S095035

S095035 will be taken orally once daily in 28-day cycle.

Study Arms ^ICMJE

Experimental: Dose Escalation

Intervention: Drug: S095035

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

May 1, 2026

Estimated Primary Completion Date

May 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Estimated life expectancy ≥3 months.
ECOG PS 0-1
Participants able to comply with highly effective method of birth control requirements.
Participants with histologically confirmed advanced or metastatic solid tumor's (excluding central nervous system tumors) that have progressed despite at least one prior treatment regimen given for advanced/metastatic disease, and for whom additional effective standard therapy is not available.
Participants with pre-existing documented MTAP homozygous deletion in their tumor tissue, determined using a next generation sequencing in vitro diagnostic test prior to screening.
Participants willing to undergo paired fresh biopsy (pre-treatment and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns.
Adequate organ functions.

Exclusion Criteria:

Inability to take an orally administered drug, or medical disorder or prior surgical resection that may affect the absorption of the study drug.
Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's Medical monitor and investigator agree and document that it should not be exclusionary.
Known prior severe hypersensitivity to any component of the study drug formulation.
Major surgery within 4 weeks prior to the first IMP administration or participants who have not recovered from side effects of the surgery.
Have a known history of Gilbert's syndrome.
Participants with a known clinically significant cardiovascular disease or condition.
Participants with thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to first IMP administration.
Active brain metastases.
Current active liver or biliary disease.
Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of S095035. Participants who have not recovered from toxicity of previous anticancer therapy.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department

+33 1 55 72 60 00

scientificinformation@servier.com

Listed Location Countries ^ICMJE

Australia, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT06188702

Other Study ID Numbers ^ICMJE

CL1-95035-001

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: sponsored by Servier with a first patient enrolled as of 1 January 2004 onwards for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Supporting Materials:	Informed Consent Form (ICF)
Supporting Materials:	Clinical Study Report (CSR)
Time Frame:	After Marketing Authorization in EEA or US if the study is used for the approval.
Access Criteria:	Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL:	http://clinicaltrials.servier.com/