A study of S095035 as a single agent and in combination in adult participants with advanced or metastatic solid tumors with deletion of MTAP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Oct 2025 → ongoing

Decision date (initial)

2025-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ADIR France · Laboratorios Servier, S. L

External identifiers

EU CT number

2025-521249-25-00

ClinicalTrials.gov

NCT06188702

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Efficacy, Others

• Phase 1: To assess the safety and tolerability, to identify the recommended dose (RD) and/or maximum tolerated dose (MTD) of S095035 as a single agent and in combinaison with TNG462 in participants with advanced or metastatic solid tumors with homozygous deletion of methylthioadenosine phosphorylase (MTAP)
• Phase 2: To assess the antitumor activity associated with S095035 as a single agent and in combinaison with TNG462 as assessed by investigator and by blinded independent central review (BICR)

Secondary objectives 6

1. Phase 1: To characterize the pharmacokinetics (PK) of S095035 (single-agent arm) and of S095035 and TNG462 (combination arm)
2. Phase 1: To characterize the pharmacodynamics (PD) of S095035 as a single agent and in combinaison with TNG462
3. Phase 1: To describe any antitumor activity associated with S095035 as a single agent and in combinaison with TNG462
4. Phase 2: To assess additional indicators of antitumor activity associated with S095035 as a single agent and in combinaison with TNG462, as assessed by investigator and BICR
5. Phase 2: To characterize the pharmacokinetics (PK) of S095035 (single-agent arms) and of S095035 and TNG462 (combination arms)
6. Phase 2: To confirm the safety, tolerability, and recommended dose (RD) of S095035 as a single agent and in combinaison with TNG462

Conditions and MedDRA coding

MTAP-deleted advanced or metastatic solid tumors

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Male or female participant aged ≥18 years of age.
2. Estimated life expectancy ≥3 months.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
4. Participants able to comply with highly effective method of birth control requirements.
5. Participants with histologically confirmed advanced or metastatic solid tumor's (excluding central nervous system tumors other than isocitrate dehydrogenase wild-type (IDHwt) glioblastoma), with measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria for participants with IDHwt glioblastoma, 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.
6. Participants with pre-existing documented methylthioadenosine phosphorylase (MTAP) homozygous gene deletion in their tumor tissue, determined using a next generation sequencing (NGS) in vitro diagnostic (IVD) test prior to screening.
7. Phase 1 only - Participants (except IDHwt glioblastoma), willing to provide newly collected tumor biopsies pre-treatment and on-treatment unless not medically feasible. Participants with IDHwt glioblastoma must provide archival tissue from their most recent surgery or biopsy, collected before screening.
8. Adequate organ functions.
9. Phase 2 only - Participants in dose expansion, except those with isocitrate dehydrogenase wild-type (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.
10. Phase 2 only - Participants with IDHwt glioblastoma must provide archival tissue from their most recent surgery or biopsy, collected before screening.
11. 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.
12. Phase 2 Arm 1b only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced BTC 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.
13. Phase 2 Arm 1c only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced PDAC 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.
14. Phase 2 Arm 1d only - Participants with locally advanced or metastatic malignancies with homozygous deletion of MTAP, with measurable disease as per RECIST version 1.1 or RANO 2.0 criteria for participants with IDHwt glioblastoma, 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.
15. Phase 2 Arm 2a only -Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced BTC with homozygous deletion of MTAP, with measurable disease as per RECIST version 1.1, 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.
16. Phase 2 Arm 2b only - Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced gastroesophageal cancer with homozygous deletion of MTAP, with measurable disease as per RECIST version 1.1, 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.
17. Phase 2 Arm 2c only -Participants with histologically or cytologically confirmed metastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP, with measurable disease as per RECIST version 1.1, 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. Participants must have exhausted available standard-of-care treatments known to be beneficial for this tumor type or would be unlikely to tolerate or derive clinically benefit from available standard-of-care therapy, and for whom this trial is a reasonable option.

Exclusion criteria 16

1. Inability to take an orally administered drug, or medical disorder or prior surgical resection that may affect the absorption of the study drug.
2. Known prior severe hypersensitivity to any component of the study drug formulation.
3. Major surgery within 4 weeks prior to the first study drug administration or participants who have not recovered from side effects of the surgery.
4. Have a known history of Gilbert’s syndrome.
5. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to first study drug intake.
6. Severe or uncontrolled active acute or chronic infection.
7. Participants who have already received a MAT2A or PRMT5 inhibitor.
8. Participants with a known clinically significant cardiovascular disease or condition.
9. Participants with thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to first study drug administration.
10. Active brain metastases.
11. Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of study drug.
12. A medical condition that results in increased clinically significant photosensitivity (e.g., solar urticaria, lupus erythematosus, etc.).
13. Pregnant or lactating women.
14. Women of childbearing potential who have a positive pregnancy test within 7 days prior to the first day of study drug administration.
15. 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.
16. Participants who are scheduled to receive the S095035–TNG462 combination, with a known clinically significant ophthalmologic disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 1: Dose-limiting toxicities (DLTs) associated with S095035 as a single agent and with S095035-TNG462 combination during the first cycle of treatment
2. Phase 1: Adverse events (AEs) and serious adverse events (SAEs), changes in safety laboratory results, changes in the physical examination, vital signs, electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status (PS)
3. Phase 2: 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 blinded independent central review (BICR): - Objective response rate (ORR)

Secondary endpoints 6

1. Phase 1 and 2: Plasma PK parameters of S095035 as a single agent and in combinaison with TNG462 including, but not limited to, AUC0 t, AUC0-∞, AUCtau,ss, Tmax, Cmax, Ctrough, t½, Vd/F, and CL/F, as data permit.
2. Phase 1: Changes from baseline in plasma concentrations of [commercially confidential information (CCI)] residues during treatment
3. Phase 1: Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria, as per investigator’s assessment: - Objective response rate (ORR) - Best overall response (BOR) - Clinical benefit rate (CBR=complete response [CR] + partial response [PR] + stable disease [SD] ≥24 weeks) - Duration of response (DOR) - Time to response (TTR)
4. Phase 2: Per RECIST version 1.1 or RANO 2.0 criteria, as assessed by investigator and blinded independent central review (BICR): - Best overall response (BOR) - Clinical benefit rate (CBR=complete response [CR] + partial response [PR] + stable disease [SD] ≥24 weeks) - Duration of response (DOR) - Time to response (TTR) - Progression-free survival (PFS) - Overall survival (OS)
5. Phase 2: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), changes in safety laboratory results, changes in the physical examination, vital signs, electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status (PS)
6. Phase 2: Frequency of dose interruptions, dose reductions, and measurements of dose intensity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 8

Locations

5 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications