S095035 for Advanced or metastatic solid tumors with homozygous MTAP deletion

Inclusion criteria

• {"criterion_text":"- Male or female participant aged ≥18 years of age."}
• {"criterion_text":"- Phase 2 only - Participants with IDHwt glioblastoma must provide archival tissue from their most recent surgery or biopsy, collected before screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Estimated life expectancy ≥3 months."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1"}
• {"criterion_text":"- Participants able to comply with highly effective method of birth control requirements."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Adequate organ functions."}
• {"criterion_text":"- 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."}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Phase 1: Dose-limiting toxicities (DLTs) associated with S095035 as a single agent and with S095035-TNG462 combination during the first cycle of treatment","definition_or_measurement_approach":"DLTs measured during the first cycle of treatment as per protocol-defined DLT criteria for Phase 1."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Safety assessed by recording AEs/SAEs, laboratory changes, physical exams, vital signs, ECGs and ECOG PS per protocol-specified schedules."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"ORR assessed by RECIST v1.1 or RANO 2.0 (for IDHwt glioblastoma) as evaluated by investigator and by blinded independent central review (BICR)."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Plasma PK parameters measured from blood samples and calculated (AUC, Tmax, Cmax, Ctrough, t½, Vd/F, CL/F) as data permit."}
• {"endpoint_text":"- Phase 1: Changes from baseline in plasma concentrations of [commercially confidential information (CCI)] residues during treatment","definition_or_measurement_approach":"Changes from baseline in specified plasma residues measured during treatment (details CCI)."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Tumor response endpoints assessed by RECIST v1.1 or RANO 2.0 per investigator: ORR, BOR, CBR (CR+PR+SD≥24w), DOR, TTR."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Tumor response and time-to-event endpoints assessed by RECIST v1.1 or RANO 2.0 per investigator and BICR: BOR, CBR, DOR, TTR, PFS, OS."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Safety assessed by incidence/severity of AEs/SAEs, labs, physical exam, vital signs, ECG, ECOG PS per protocol."}
• {"endpoint_text":"- Phase 2: Frequency of dose interruptions, dose reductions, and measurements of dose intensity","definition_or_measurement_approach":"Recorded frequency of dose interruptions/reductions and dose intensity metrics during treatment."}

Spain

Earliest CTIS Part Ii Submission Date

11-09-2025

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

208

Number Of Sites

4

Number Of Participants

24

Germany

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

207

Number Of Sites

4

Number Of Participants

22

Italy

Earliest CTIS Part Ii Submission Date

17-09-2025

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

196

Number Of Sites

4

Number Of Participants

25

Denmark

Earliest CTIS Part Ii Submission Date

11-09-2025

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

202

Number Of Sites

2

Number Of Participants

10

France

Earliest CTIS Part Ii Submission Date

12-09-2025

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

222

Number Of Sites

4

Number Of Participants

23

Primary sponsor

Full Name

Institut De Recherches Internationales Servier IRIS

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

IQVIA Limited

Name

Ppd Inc.

Responsibilities

PK/PD

Name

Biotrial

Responsibilities

ECG, MRI and CT/PET Scan Central reading

Third parties

• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"Biomarker: NGS","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Biotrial","duties_or_roles":"ECG, MRI and CT/PET Scan Central reading","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"C.D.L. Pharma S.A.S.","duties_or_roles":"Central Lab Logistics","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long term storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"PK/PD","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Biomarker: ctDNA","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"CellCarta Lake Forest","duties_or_roles":"Biomarker: Immunohistochemistry","organisation_type":"Industry"}