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

NCT06188702 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CL1-95035-0012025-521249-25-00
• Study Type: interventional
• Target: 342
• Locations: 8 countries
• Sites: 35

Brief Summary

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.

Conditions

MTAP-deleted Solid Tumors

Keywords

MAT2A; MTAP; Solid Tumors; PRMT5; SAM; Synthetic Lethality; MTAP deletion; MAT2A Inhibitor; Advanced Solid Tumors; Biliary Tract Cancer; Non-small Cell Lung Cancer; Pancreatic Adenocarcinoma; Gastroesophageal Cancer

Outcome Measures

Primary Outcomes (4)

• Dose limiting toxicities (DLTs)

  Phase 1 only

  Through cycle 1 (each cycle is 28 days)

• Total number of adverse events (AEs)

  Phase 1 only

  Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years

• Total number of serious adverse events (SAEs)

  Phase 1 only

  Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years

• Objective response rate (ORR)

  Phase 2 only; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment and by blinded independent central review (BICR)

  Through the end of the study (approximately 5 years)

Secondary Outcomes (22)

• Area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t)

  Through the last dose of study treatment (approximately 5 years)

• AUC from 0 to infinity (AUC0-∞)

  Through the last dose of study treatment (approximately 5 years)

• AUC over 1 dosing interval at steady state (AUCtau,ss)

  Through the last dose of study treatment (approximately 5 years)

• Time to maximum concentration (Tmax)

  Through the last dose of study treatment (approximately 5 years)

• Maximum concentration (Cmax)

  Through the last dose of study treatment (approximately 5 years)

Study Arms (9)

Phase 1 Arm 1 - S095035 single-agent dose escalation

EXPERIMENTAL

Drug: S095035

Phase 1 Arm 2 - S095035-TNG462 combination dose escalation

EXPERIMENTAL

Drug: S095035; Drug: TNG462

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

EXPERIMENTAL

Non-Small Cell Lung Cancer

Drug: S095035

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

EXPERIMENTAL

Biliary Tract Cancer

Drug: S095035

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

EXPERIMENTAL

Pancreatic Ductal Adenocarcinoma

Drug: S095035

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

EXPERIMENTAL

Drug: S095035

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

EXPERIMENTAL

Biliary Tract Cancer

Drug: S095035; Drug: TNG462

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

EXPERIMENTAL

Drug: S095035; Drug: TNG462

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

EXPERIMENTAL

Pancreatic Ductal Adenocarcinoma

Drug: S095035; Drug: TNG462

Interventions

S095035 DRUG

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

Phase 1 Arm 1 - S095035 single-agent dose escalation; Phase 1 Arm 2 - S095035-TNG462 combination dose escalation; Phase 2 Arm 1a NSCLC - S095035 single-agent dose expansion; Phase 2 Arm 1b BTC - S095035 single-agent dose expansion; Phase 2 Arm 1c PDAC - S095035 single-agent dose expansion; Phase 2 Arm 1d Basket arm - S095035 single-agent dose expansion; Phase 2 Arm 2a BTC - S095035-TNG462 combination dose expansion; Phase 2 Arm 2b Gastroesophageal - S095035-TNG462 combination dose expansion; Phase 2 Arm 2c PDAC - S095035-TNG462 combination dose expansion

TNG462 DRUG

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

Phase 1 Arm 2 - S095035-TNG462 combination dose escalation; Phase 2 Arm 2a BTC - S095035-TNG462 combination dose expansion; Phase 2 Arm 2b Gastroesophageal - S095035-TNG462 combination dose expansion; Phase 2 Arm 2c PDAC - S095035-TNG462 combination dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Inability to take an orally administered drug, or medical disorder or prior surgical resection that may affect the absorption of the study drug.
• 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:

Sponsors & Collaborators

• Servier Bio-Innovation LLC: lead
• Institut de Recherches Internationales Servier: collaborator
• Tango Therapeutics, Inc.: collaborator

Study Sites (35)

University of California Los Angeles

Los Angeles, California, 90095, United States

NOT YET RECRUITING

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

San Francisco, California, 94143, United States

NOT YET RECRUITING

Lake Mary Cancer Center - Florida Cancer Specialists & Research Institute

Lake Mary, Florida, 32746, United States

TERMINATED

Community Health Network

Indianapolis, Indiana, 46250, United States

RECRUITING

Dana Farber Cancer Institue

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Duke University School of Medicine

Durham, North Carolina, 27710, United States

NOT YET RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Oncology

Austin, Texas, 78758, United States

RECRUITING

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

RECRUITING

The Alfred

Prahran, Victoria, 3004, Australia

RECRUITING

Townsville University Hospital

Douglas, 4812, Australia

RECRUITING

Royal Hobart Hospital

Hobart, 7000, Australia

SUSPENDED

University Hospital Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Odense Universitets Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

Institut Bergonié

Bordeaux, 33076, France

NOT YET RECRUITING

Centre Georges-François Leclerc

Dijon, 21079, France

RECRUITING

Hôpital de la Timone (Marseille)

Marseille, 13385, France

RECRUITING

Institut Gustave Roussy

Paris, 94805, France

RECRUITING

Charite Universitatsmedizin

Berlin, 13353, Germany

NOT YET RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

NOT YET RECRUITING

Med Fakultaet Heidelberg

Heidelberg, 69120, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

Istituto Europeo Di Oncologia

Milan, 20141, Italy

NOT YET RECRUITING

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

Naples, 80131, Italy

NOT YET RECRUITING

Ist. Nazionale Tumori Irccs Fondazione G Pascale

Naples, 80131, Italy

RECRUITING

Instituto Clinico Humanitas Irccs

Rozzano, 20098, Italy

RECRUITING

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

Verona, 37134, Italy

RECRUITING

Aichi Cancer Center

Aichi, 4648681, Japan

RECRUITING

National Hospital Organization Shikoku Cancer Center

Ehime, 7910280, Japan

RECRUITING

The Cancer Institute Hospital of JFCR

Tokyo, 1358550, Japan

RECRUITING

Next Oncology-Hospital Quironsalud Barcelona

Barcelona, 8023, Spain

RECRUITING

Hospital Vall D'Hebron

Barcelona, 8035, Spain

NOT YET RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Start Madrid Group - Hm Ciocc

Madrid, 28050, Spain

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

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

CONTACT

+33 1 55 72 60 00; scientificinformation@servier.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 3, 2024
• Study Start: April 29, 2024
• Primary Completion (Estimated): October 31, 2031
• Study Completion (Estimated): October 31, 2031
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

ES (4); DE (4); AU (4); US (9); DK (2); FR (4); IT (5); JP (3)