A Phase I/II, 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

Study Identifier:
CL1-95035-001
CT.gov Identifier:
NCT06188702
EudraCT Identifier:
202552000000
EU Trial (CTIS) Number:
2025-521249-25-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
    N/A
    Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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. Patients in China with IDHwt glioblastoma will not be included.
    • 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 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.
    • Phase 2 only - Participants with IDHwt glioblastoma must provide archival tissue from their most recent surgery or biopsy, collected before screening.
    • Phase 2 only - Participants in China who are to be considered for enrollment in the single agent dose expansion Arms and who have a pre-existing, documented cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous gene deletion in their tumor tissue (confirmed by an NGS IVD test), but do not have homozygous MTAP deletion reported, will need to be pre-screened to confirm homozygous MTAP deletion. Pre screening for homozygous MTAP deletion will be conducted using a central NGS IVD test using an archival tumor tissue, preferably the most recent and not older than 3 years.
    • 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.
    • 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 in the advanced/metastatic setting.
    • 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 in the advanced/metastatic setting.
    • 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 in the advanced/metastatic setting.
    • 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 in the advanced/metastatic setting.
    • 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 in the advanced/metastatic setting.
    • 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 in the advanced/metastatic setting
    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.).
    • Participants who are scheduled to receive the S095035-TNG462 combination, with a known clinically significant ophthalmologic disease, including:
    • Prior history of drug-induced or toxic retinopathy or optic neuropathy
    • Uncontrolled glaucoma
    • Pre-existing macular degeneration
    • Ongoing Grade ≥2 retinopathy, optic neuropathy, or optic neuritis
    • Other known active retinal pathology

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruitment on Hold
    Condition(s) Treated at Site
    Solid Tumor