S095035 in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of the Methylthioadenosine Phosphorylase (MTAP) Gene
- Registration Number
- NCT06188702
- Lead Sponsor
- Servier Bio-Innovation LLC
- Brief Summary
This is a first-in-human Phase 1, multicenter, open-label dose escalation study of S095035 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 27
- 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) 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.
- Participants with pre-existing documented MTAP homozygous deletion in their tumor tissue, determined using a next generation sequencing in vitro diagnostic test prior to screening.
- Participants willing to undergo paired fresh biopsy (pre-treatment and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns.
- Adequate organ functions.
- 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 IMP 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.
- Current active liver or biliary disease.
- Participants who have received systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of S095035. Participants who have not recovered from toxicity of previous anticancer therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation S095035 -
- Primary Outcome Measures
Name Time Method Total number of adverse events (AEs) Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) Dose limiting toxicities (DLTs) associated with S095035 administration during the first cycle of treatment Through cycle 1 (each cycle is 28 days) Total number of serious adverse events (SAEs) Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment)
- Secondary Outcome Measures
Name Time Method Apparent clearance (CL/F) Through the last dose of study treatment (approximately 2 years) Change from baseline in plasma concentrations of S-adenosylmethionine (SAM) Through the last dose of study treatment (approximately 2 years) Clinical benefit rate (CBR) Through the end of the study (approximately 2 years) CBR=complete response \[CR\]+partial response \[PR\]+stable disease \[SD\] ) ≥6 months, Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment
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 2 years) AUC from 0 to infinity (AUC0-∞) Through the last dose of study treatment (approximately 2 years) AUC over 1 dosing interval at steady state (AUCtau,ss) Through the last dose of study treatment (approximately 2 years) Time to maximum concentration (Tmax) Through the last dose of study treatment (approximately 2 years) Maximum concentration (Cmax) Through the last dose of study treatment (approximately 2 years) Trough concentration (Ctrough) Through the last dose of study treatment (approximately 2 years) Half-life (t½) Through the last dose of study treatment (approximately 2 years) Apparent volume of distribution (Vd/F) Through the last dose of study treatment (approximately 2 years) Objective response rate Through the end of the study (approximately 2 years) Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment
Duration of response Through the end of the study (approximately 2 years) Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment. 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.
Time to response Through the end of the study (approximately 2 years) Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and per the investigator's assessment. The time from the date of randomization to date of first documented confirmed complete response (CR) or confirmed partial response (PR).
Trial Locations
- Locations (11)
Lake Mary Cancer Center - Florida Cancer Specialists & Research Institute
🇺🇸Lake Mary, Florida, United States
Community Health Network
🇺🇸Indianapolis, Indiana, United States
Taylor Cancer Research Center
🇺🇸Maumee, Ohio, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
NEXT Oncology
🇺🇸Austin, Texas, United States
Scientia Clinical Research
🇦🇺Randwick, New South Wales, Australia
The Alfred
🇦🇺Prahran, Victoria, Australia
Townsville University Hospital
🇦🇺Douglas, Australia
Aichi Cancer Center
🇯🇵Aichi, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Ehime, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan