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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
342
S095035 will be taken orally every day in 28-day cycles.
TNG462 will be taken orally every day in 28-day cycles.
University of California Los Angeles
Los Angeles, California, United States
NOT_YET_RECRUITINGUniversity of California, San Francisco (Ucsf) School of Medicine
San Francisco, California, United States
NOT_YET_RECRUITINGLake Mary Cancer Center - Florida Cancer Specialists & Research Institute
Lake Mary, Florida, United States
RECRUITINGCommunity Health Network
Indianapolis, Indiana, United States
Dose limiting toxicities (DLTs)
Phase 1 only
Time frame: Through cycle 1 (each cycle is 28 days)
Total number of adverse events (AEs)
Phase 1 only
Time frame: 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)
Phase 1 only
Time frame: Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Objective response rate (ORR)
Phase 2 only; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment and by blinded independent central review (BICR)
Time frame: Through the end of the study (approximately 5 years)
Area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
AUC from 0 to infinity (AUC0-∞)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
AUC over 1 dosing interval at steady state (AUCtau,ss)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Time to maximum concentration (Tmax)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Maximum concentration (Cmax)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Trough concentration (Ctrough)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Half-life (t½)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Apparent volume of distribution (Vd/F)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Apparent clearance (CL/F)
Phase 1 and 2
Time frame: Through the last dose of study treatment (approximately 5 years)
Change from baseline in plasma concentrations of S-adenosylmethionine (SAM) and/or tumor symmetric dimethylarginine (SDMA) residues during treatment
Phase 1 only
Time frame: Through the last dose of study treatment (approximately 5 years)
Objective response rate (ORR)
Phase 1 only; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment
Time frame: Through the end of the study (approximately 5 years)
Best overall response (BOR)
Phase 1 and 2; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment for Phase 1 and 2, and by BICR only for Phase 2.
Time frame: Through the end of the study (approximately 5 years)
Clinical benefit rate (CBR)
Phase 1 and 2; CBR=complete response \[CR\]+partial response \[PR\]+stable disease \[SD\] ) ≥6 months, Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment for Phase 1 and 2, and by BICR only for Phase 2
Time frame: Through the end of the study (approximately 5 years)
Duration of response (DOR)
Phase 1 and 2; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment for Phase 1 and 2, and by BICR only for Phase 2. 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 frame: Through the end of the study (approximately 5 years)
Time to response (TTR)
Phase 1 and 2; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment for Phase 1 and 2, and by BICR only for Phase 2. The time from the date of randomization to date of first documented confirmed complete response (CR) or confirmed partial response (PR).
Time frame: Through the end of the study (approximately 5 years)
Progression-free Survival (PFS)
Phase 2 Only; 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 BICR
Time frame: Through the end of the study (approximately 5 years)
Overall Survival (OS)
Phase 2 Only; 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 BICR
Time frame: Through the end of the study (approximately 5 years)
Total number of adverse events (AEs)
Phase 2 Only
Time frame: 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)
Phase 2 Only
Time frame: Through the Safety Follow-up Visit (until 30 days after the last dose of study treatment) approximately 5 years
Number of dose interruptions
Phase 2 Only
Time frame: Through the last dose of study treatment (approximately 5 years)
Number of dose reductions
Phase 2 Only
Time frame: Through the last dose of study treatment (approximately 5 years)
Dose intensity
Phase 2 Only
Time frame: Through the last dose of study treatment (approximately 5 years)
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
CONTACT
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