S095035 As A Single Agent And In Combination In Adult Participants With Advanced Or Metastatic Solid Tumors With Deletion Of MTAP

Study Overview

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

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.

N/A

MTAP-deleted Solid Tumors

DRUG: S095035
DRUG: TNG462

CL1-95035-001
2025-521249-25-00 (CTIS Identifier) (CTIS: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-12-18	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-13
First Submitted that Met QC Criteria 2024-01-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-17
First Posted (ACTUAL) 2024-01-03	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1 Arm 1 - S095035 single-agent dose escalation	DRUG: S095035 S095035 will be taken orally once daily in 28-day cycles.
EXPERIMENTAL: Phase 1 Arm 2 - S095035-TNG462 combination dose escalation	DRUG: S095035 S095035 will be taken orally once daily in 28-day cycles. DRUG: TNG462 TNG462 will be taken orally once daily in 28-day cycles.
EXPERIMENTAL: Phase 2 Arm 1a NSCLC - S095035 single-agent dose expansion Non-Small Cell Lung Cancer	DRUG: S095035 S095035 will be taken orally once daily in 28-day cycles.
EXPERIMENTAL: Phase 2 Arm 1b BTC - S095035 single-agent dose expansion Biliary Tract Cancer	DRUG: S095035 S095035 will be taken orally once daily in 28-day cycles.
EXPERIMENTAL: Phase 2 Arm 1c PDAC - S095035 single-agent dose expansion Pancreatic Ductal Adenocarcinoma
EXPERIMENTAL: Phase 2 Arm 1d Basket arm - S095035 single-agent dose expansion
EXPERIMENTAL: Phase 2 Arm 2a BTC - S095035-TNG462 combination dose expansion Biliary Tract Cancer	DRUG: TNG462 TNG462 will be taken orally once daily in 28-day cycles.
EXPERIMENTAL: Phase 2 Arm 2b Gastroesophageal - S095035-TNG462 combination dose expansion	DRUG: TNG462 TNG462 will be taken orally once daily in 28-day cycles.
EXPERIMENTAL: Phase 2 Arm 2c PDAC - S095035-TNG462 combination dose expansion Pancreatic Ductal Adenocarcinoma

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
AUC from 0 to infinity (AUC0-∞)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
AUC over 1 dosing interval at steady state (AUCtau,ss)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Time to maximum concentration (Tmax)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Maximum concentration (Cmax)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Trough concentration (Ctrough)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Half-life (t½)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Apparent volume of distribution (Vd/F)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Apparent clearance (CL/F)	Phase 1 and 2	Through the last dose of study treatment (approximately 5 years)
Change from baseline in plasma concentrations of S-adenosylmethionine (SAM) and/or tumor symmetric dimethylarginine (SDMA) residues during treatment	Phase 1 only	Through the last dose of study treatment (approximately 5 years)
Objective response rate (ORR)	Phase 1 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	Through the end of the study (approximately 5 years)
Best overall response (BOR)	Phase 1 and 2; 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 for Phase 1 and 2, and by BICR only for Phase 2.	Through the end of the study (approximately 5 years)
Clinical benefit rate (CBR)	Phase 1 and 2; CBR=complete response [CR]+partial response [PR]+stable disease [SD] ) ≥6 months, 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 for Phase 1 and 2, and by BICR only for Phase 2	Through the end of the study (approximately 5 years)
Duration of response (DOR)	Phase 1 and 2; 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 for Phase 1 and 2, and by BICR only for Phase 2. 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.	Through the end of the study (approximately 5 years)
Time to response (TTR)	Phase 1 and 2; 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 for Phase 1 and 2, and by BICR only for Phase 2. The time from the date of randomization to date of first documented confirmed complete response (CR) or confirmed partial response (PR).	Through the end of the study (approximately 5 years)
Progression-free Survival (PFS)	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 assessed by investigator and by BICR	Through the end of the study (approximately 5 years)
Overall Survival (OS)	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 assessed by investigator and by BICR	Through the end of the study (approximately 5 years)
Total number of adverse events (AEs)	Phase 2 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 2 Only	Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Number of dose interruptions	Phase 2 Only	Through the last dose of study treatment (approximately 5 years)
Number of dose reductions	Phase 2 Only	Through the last dose of study treatment (approximately 5 years)
Dose intensity	Phase 2 Only	Through the last dose of study treatment (approximately 5 years)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

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

Phone Number: +33 1 55 72 60 00

Email: scientificinformation@servier.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.
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 it is not medically feasible, then archival tissue is acceptable if 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, even if that occurred >3 months before study entry.
Phase 2 Arm 1a only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC 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.
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.
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.
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.
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.
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.
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.

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.).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Institut de Recherches Internationales Servier
Tango Therapeutics, Inc.

Investigators

Publications

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