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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06188702




Registration number
NCT06188702
Ethics application status
Date submitted
18/12/2023
Date registered
3/01/2024
Date last updated
17/06/2025

Titles & IDs
Public title
S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP
Scientific title
A Phase 1/2, Open-label, Multicenter Clinical Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Antineoplastic Activity of S095035 (MAT2A Inhibitor) as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Homozygous Deletion of MTAP
Secondary ID [1] 0 0
2025-521249-25-00
Secondary ID [2] 0 0
CL1-95035-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
MTAP-deleted Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - S095035
Treatment: Drugs - TNG462

Experimental: Phase 1 Arm 1 - S095035 single-agent dose escalation -

Experimental: Phase 1 Arm 2 - S095035-TNG462 combination dose escalation -

Experimental: Phase 2 Arm 1a NSCLC - S095035 single-agent dose expansion - Non-Small Cell Lung Cancer

Experimental: Phase 2 Arm 1b BTC - S095035 single-agent dose expansion - Biliary Tract Cancer

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

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

Experimental: Phase 2 Arm 2c PDAC - S095035-TNG462 combination dose expansion - Pancreatic Ductal Adenocarcinoma


Treatment: Drugs: S095035
S095035 will be taken orally once daily in 28-day cycles.

Treatment: Drugs: TNG462
TNG462 will be taken orally once daily in 28-day cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicities (DLTs)
Timepoint [1] 0 0
Through cycle 1 (each cycle is 28 days)
Primary outcome [2] 0 0
Total number of adverse events (AEs)
Timepoint [2] 0 0
Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Primary outcome [3] 0 0
Total number of serious adverse events (SAEs)
Timepoint [3] 0 0
Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Primary outcome [4] 0 0
Objective response rate (ORR)
Timepoint [4] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [1] 0 0
Area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t)
Timepoint [1] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [2] 0 0
AUC from 0 to infinity (AUC0-8)
Timepoint [2] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [3] 0 0
AUC over 1 dosing interval at steady state (AUCtau,ss)
Timepoint [3] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [4] 0 0
Time to maximum concentration (Tmax)
Timepoint [4] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [5] 0 0
Maximum concentration (Cmax)
Timepoint [5] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [6] 0 0
Trough concentration (Ctrough)
Timepoint [6] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [7] 0 0
Half-life (t½)
Timepoint [7] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [8] 0 0
Apparent volume of distribution (Vd/F)
Timepoint [8] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [9] 0 0
Apparent clearance (CL/F)
Timepoint [9] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [10] 0 0
Change from baseline in plasma concentrations of S-adenosylmethionine (SAM) and/or tumor symmetric dimethylarginine (SDMA) residues during treatment
Timepoint [10] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [11] 0 0
Objective response rate (ORR)
Timepoint [11] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [12] 0 0
Best overall response (BOR)
Timepoint [12] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [13] 0 0
Clinical benefit rate (CBR)
Timepoint [13] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [14] 0 0
Duration of response (DOR)
Timepoint [14] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [15] 0 0
Time to response (TTR)
Timepoint [15] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [16] 0 0
Progression-free Survival (PFS)
Timepoint [16] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [17] 0 0
Overall Survival (OS)
Timepoint [17] 0 0
Through the end of the study (approximately 5 years)
Secondary outcome [18] 0 0
Total number of adverse events (AEs)
Timepoint [18] 0 0
Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Secondary outcome [19] 0 0
Total number of serious adverse events (SAEs)
Timepoint [19] 0 0
Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Secondary outcome [20] 0 0
Number of dose interruptions
Timepoint [20] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [21] 0 0
Number of dose reductions
Timepoint [21] 0 0
Through the last dose of study treatment (approximately 5 years)
Secondary outcome [22] 0 0
Dose intensity
Timepoint [22] 0 0
Through the last dose of study treatment (approximately 5 years)

Eligibility
Key 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.
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2031
Actual
Sample size
Target
308
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Scientia Clinical Research - Randwick
Recruitment hospital [2] 0 0
The Alfred - Prahran
Recruitment hospital [3] 0 0
Townsville University Hospital - Douglas
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3004 - Prahran
Recruitment postcode(s) [3] 0 0
4812 - Douglas
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Denmark
State/province [8] 0 0
Copenhagen
Country [9] 0 0
Denmark
State/province [9] 0 0
Odense
Country [10] 0 0
France
State/province [10] 0 0
Bordeaux
Country [11] 0 0
France
State/province [11] 0 0
Dijon
Country [12] 0 0
France
State/province [12] 0 0
Toulouse
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Düsseldorf
Country [15] 0 0
Germany
State/province [15] 0 0
Heidelberg
Country [16] 0 0
Germany
State/province [16] 0 0
Ulm
Country [17] 0 0
Italy
State/province [17] 0 0
Milano
Country [18] 0 0
Italy
State/province [18] 0 0
Napoli
Country [19] 0 0
Italy
State/province [19] 0 0
Rozzano
Country [20] 0 0
Italy
State/province [20] 0 0
Verona
Country [21] 0 0
Japan
State/province [21] 0 0
Aichi
Country [22] 0 0
Japan
State/province [22] 0 0
Ehime
Country [23] 0 0
Japan
State/province [23] 0 0
Tokyo
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Servier Bio-Innovation LLC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Institut de Recherches Internationales Servier
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Tango Therapeutics, Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
Address 0 0
Country 0 0
Phone 0 0
+33 1 55 72 60 00
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06188702