TrialPath
← Back to searchRecruiting

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP

NCT06188702 · Servier
In plain English

Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.

Official 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
About this study
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.
Eligibility criteria
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
Study design
Enrollment target: 342 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-04-29
Estimated completion: 2031-10-31
Last updated: 2026-04-03
Interventions
Drug: S095035Drug: TNG462
Primary outcomes
  • Dose limiting toxicities (DLTs) (Through cycle 1 (each cycle is 28 days))
  • Total number of adverse events (AEs) (Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years)
  • Total number of serious adverse events (SAEs) (Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years)
Sponsor
Servier Bio-Innovation LLC · industry
With: Institut de Recherches Internationales Servier, Tango Therapeutics, Inc.
Contacts & investigators
ContactInstitut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department · contact · scientificinformation@servier.com · +33 1 55 72 60 00
All locations (35)
University of California Los AngelesNot Yet Recruiting
Los Angeles, California, United States
University of California, San Francisco (Ucsf) School of MedicineNot Yet Recruiting
San Francisco, California, United States
Lake Mary Cancer Center - Florida Cancer Specialists & Research InstituteTerminated
Lake Mary, Florida, United States
Community Health NetworkRecruiting
Indianapolis, Indiana, United States
Dana Farber Cancer InstitueNot Yet Recruiting
Boston, Massachusetts, United States
Duke University School of MedicineNot Yet Recruiting
Durham, North Carolina, United States
Taylor Cancer Research CenterRecruiting
Maumee, Ohio, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
NEXT OncologyRecruiting
Austin, Texas, United States
Scientia Clinical ResearchRecruiting
Randwick, New South Wales, Australia
The AlfredRecruiting
Prahran, Victoria, Australia
Townsville University HospitalRecruiting
Douglas, Australia
Royal Hobart HospitalSuspended
Hobart, Australia
University Hospital RigshospitaletNot Yet Recruiting
Copenhagen, Denmark
Odense Universitets HospitalRecruiting
Odense, Denmark
Institut BergoniéRecruiting
Bordeaux, France
Centre Georges-François LeclercRecruiting
Dijon, France
Hôpital de la Timone (Marseille)Recruiting
Marseille, France
Institut Gustave RoussyRecruiting
Paris, France
Charite UniversitatsmedizinNot Yet Recruiting
Berlin, Germany
Universitätsklinikum DüsseldorfRecruiting
Düsseldorf, Germany
Med Fakultaet HeidelbergNot Yet Recruiting
Heidelberg, Germany
Universitätsklinikum UlmRecruiting
Ulm, Germany
Istituto Europeo Di OncologiaNot Yet Recruiting
Milan, Italy
A.O.U. Seconda Università Degli Studi Di NapoliRecruiting
Naples, Italy
Ist. Nazionale Tumori Irccs Fondazione G PascaleRecruiting
Naples, Italy
Instituto Clinico Humanitas IrccsRecruiting
Rozzano, Italy
Policlinico G.B. Rossi A.O.U.I. Di VeronaRecruiting
Verona, Italy
Aichi Cancer CenterRecruiting
Aichi, Japan
National Hospital Organization Shikoku Cancer CenterRecruiting
Ehime, Japan
The Cancer Institute Hospital of JFCRRecruiting
Tokyo, Japan
Next Oncology-Hospital Quironsalud BarcelonaRecruiting
Barcelona, Spain
Hospital Vall D'HebronRecruiting
Barcelona, Spain
Hospital Universitario Fundación Jiménez DíazRecruiting
Madrid, Spain
Start Madrid Group - Hm CioccRecruiting
Madrid, Spain
S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP · TrialPath