S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP

NCT ID: NCT06188702

Last Updated: 2026-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

342 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-29

Study Completion Date

2031-10-31

Brief Summary

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This is a first-in-human Phase 1/2, multicenter, open-label study of S095035 as single-agent, or in combination with TNG462 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. TNG462 is a protein arginine N-methyltransferase 5 \[PRMT5\] inhibitor.

Detailed Description

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Conditions

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MTAP-deleted Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1 Arm 1 - S095035 single-agent dose escalation

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

Phase 1 Arm 2 - S095035-TNG462 combination dose escalation

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

TNG462

Intervention Type DRUG

TNG462 will be taken orally every day in 28-day cycles.

Phase 2 Arm 1a NSCLC - S095035 single-agent dose expansion

Non-Small Cell Lung Cancer

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

Phase 2 Arm 1b BTC - S095035 single-agent dose expansion

Biliary Tract Cancer

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

Phase 2 Arm 1c PDAC - S095035 single-agent dose expansion

Pancreatic Ductal Adenocarcinoma

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

Phase 2 Arm 1d Basket arm - S095035 single-agent dose expansion

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

Phase 2 Arm 2a BTC - S095035-TNG462 combination dose expansion

Biliary Tract Cancer

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

TNG462

Intervention Type DRUG

TNG462 will be taken orally every day in 28-day cycles.

Phase 2 Arm 2b Gastroesophageal - S095035-TNG462 combination dose expansion

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

TNG462

Intervention Type DRUG

TNG462 will be taken orally every day in 28-day cycles.

Phase 2 Arm 2c PDAC - S095035-TNG462 combination dose expansion

Pancreatic Ductal Adenocarcinoma

Group Type EXPERIMENTAL

S095035

Intervention Type DRUG

S095035 will be taken orally every day in 28-day cycles.

TNG462

Intervention Type DRUG

TNG462 will be taken orally every day in 28-day cycles.

Interventions

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S095035

S095035 will be taken orally every day in 28-day cycles.

Intervention Type DRUG

TNG462

TNG462 will be taken orally every day in 28-day cycles.

Intervention Type DRUG

Eligibility Criteria

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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 other than IDHwt glioblastoma), with measurable disease as per RECIST 1.1 or RANO 2.0 criteria for participants with IDHwt glioblastoma, that have progressed after at least one prior treatment regimen given for advanced/metastatic disease, and for whom additional effective standard therapy is not available. Patients in China with IDHwt glioblastoma will not be included.
* Participants with pre-existing documented MTAP homozygous gene deletion in their tumor tissue, determined using a next generation sequencing in vitro diagnostic test prior to screening.
* Phase 1 only - Participants (except IDHwt glioblastoma) willing to undergo paired fresh biopsy (pre-treatment and on-treatment) procedure. Exceptions may be made for feasibility and safety concerns. IDHwt glioblastoma must provide archival tissue from most recent surgery or biopsy.
* Adequate organ functions.
* Phase 2 only - Participants in dose expansion, except those with IDHwt glioblastoma, must provide newly collected tumor biopsies at screening. If not medically feasible archival tissue may be used, provided it was collected within 3 months before study entry and no treatment has been received since the most recent biopsy.
* Phase 2 only - Participants with IDHwt glioblastoma must provide archival tissue from their most recent surgery or biopsy, collected before screening.
* Phase 2 only - Participants in China who are to be considered for enrollment in the single agent dose expansion Arms and who have a pre-existing, documented cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous gene deletion in their tumor tissue (confirmed by an NGS IVD test), but do not have homozygous MTAP deletion reported, will need to be pre-screened to confirm homozygous MTAP deletion. Pre screening for homozygous MTAP deletion will be conducted using a central NGS IVD test using an archival tumor tissue, preferably the most recent and not older than 3 years.
* Phase 2 Arm 1a only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with homozygous deletion of MTAP, with measurable disease as per RECIST version 1.1, who have progressed or experienced disease recurrence during or after at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 1b only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced BTC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 1c only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 1d only - Participants with any other locally advanced or metastatic malignancies with homozygous deletion of MTAP, who have received and progressed of experienced recurrence during or after receiving at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 2a only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced BTC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after receiving at least 1 prior line of standard-of care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 2b only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced gastroesophageal cancer with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after receiving at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.
* Phase 2 Arm 2c only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP, who have progressed or experienced disease recurrence during or after receiving at least 1 prior line of standard-of-care systemic therapy in the advanced/metastatic setting.

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 study drug 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.
* Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of study drug
* Pregnant or lactating women.
* Women of childbearing potential who have a positive pregnancy test within 7 days prior to the first day of study drug administration.
* History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to first study drug intake.
* Severe or uncontrolled active acute or chronic infection.
* Participants who have already received a MAT2A or PRMT5 inhibitor.
* A medical condition that results in increased clinically significant photosensitivity (e.g., solar urticaria, lupus erythematosus, etc.).
* Participants who are scheduled to receive the S095035-TNG462 combination, with a known clinically significant ophthalmologic disease, including:
* Prior history of drug-induced or toxic retinopathy or optic neuropathy
* Uncontrolled glaucoma
* Pre-existing macular degeneration
* Ongoing Grade ≥2 retinopathy, optic neuropathy, or optic neuritis
* Other known active retinal pathology
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut de Recherches Internationales Servier

OTHER

Sponsor Role collaborator

Tango Therapeutics, Inc.

INDUSTRY

Sponsor Role collaborator

Servier Bio-Innovation LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California Los Angeles

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

University of California, San Francisco (Ucsf) School of Medicine

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

Lake Mary Cancer Center - Florida Cancer Specialists & Research Institute

Lake Mary, Florida, United States

Site Status RECRUITING

Community Health Network

Indianapolis, Indiana, United States

Site Status RECRUITING

Dana Farber Cancer Institue

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Duke University School of Medicine

Durham, North Carolina, United States

Site Status NOT_YET_RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

NEXT Oncology

Austin, Texas, United States

Site Status RECRUITING

Scientia Clinical Research

Randwick, New South Wales, Australia

Site Status RECRUITING

The Alfred

Prahran, Victoria, Australia

Site Status RECRUITING

Townsville University Hospital

Douglas, , Australia

Site Status RECRUITING

Royal Hobart Hospital

Hobart, , Australia

Site Status SUSPENDED

University Hospital Rigshospitalet

Copenhagen, , Denmark

Site Status NOT_YET_RECRUITING

Odense Universitets Hospital

Odense, , Denmark

Site Status NOT_YET_RECRUITING

Institut Bergonié

Bordeaux, , France

Site Status NOT_YET_RECRUITING

Centre Georges-François Leclerc

Dijon, , France

Site Status RECRUITING

Charite Universitatsmedizin

Berlin, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status NOT_YET_RECRUITING

Med Fakultaet Heidelberg

Heidelberg, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Ulm

Ulm, , Germany

Site Status RECRUITING

Istituto Europeo Di Oncologia

Milan, , Italy

Site Status NOT_YET_RECRUITING

A.O.U. Seconda Università Degli Studi Di Napoli

Napoli, , Italy

Site Status NOT_YET_RECRUITING

Ist. Nazionale Tumori Irccs Fondazione G Pascale

Napoli, , Italy

Site Status NOT_YET_RECRUITING

Instituto Clinico Humanitas Irccs

Rozzano, , Italy

Site Status RECRUITING

Policlinico G.B. Rossi A.O.U.I. Di Verona

Verona, , Italy

Site Status RECRUITING

Aichi Cancer Center

Aichi, , Japan

Site Status RECRUITING

National Hospital Organization Shikoku Cancer Center

Ehime, , Japan

Site Status RECRUITING

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status RECRUITING

Next Oncology-Hospital Quironsalud Barcelona

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital Vall D'Hebron

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status RECRUITING

Start Madrid Group - Hm Ciocc

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Australia Denmark France Germany Italy Japan Spain

Central Contacts

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

Role: CONTACT

+33 1 55 72 60 00

Other Identifiers

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2025-521249-25-00

Identifier Type: CTIS

Identifier Source: secondary_id

CL1-95035-001

Identifier Type: -

Identifier Source: org_study_id

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