Study of FIH of STX-241 in Locally Advanced or Metastatic NSCLC Resistant to EGFR TKIs
NCT Number: NCT06567015
Acronym: STX-241 FIH
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Non-small Cell Lung Cancer (NSCLC)
Interventions: DRUG: STX-241
Sponsor: Pierre Fabre Medicament
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 171
Study Design: Allocation: NA|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-05
Completion Date: 2030-07
Locations: Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium), Nashville, Tennessee, 37203, United States|Shanghai East Hospital, Tongji University, Shanghai, 200120, China|Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China|Centre Léon Bérard, Lyon, 69008, France|CHU Hôpital de la Timone, Marseille, 13385, France|Institut de Cancérologie de l'Ouest (ICO) - René Gauducheau, Saint-Herblain, 44800, France|Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, 31059, France|Gustave Roussy, Villejuif, 94800, France|Universitätsklinikum Carl Gustav Carus Dresden, Dresden, 1307, Germany|Netherlands Cancer Institute, Amsterdam, 1066 CX, Netherlands|Vall d'Hebron Institut d'Oncologia, Barcelona, 8035, Spain|Hospital Universitario La Paz, Madrid, 28046, Spain|Centro Integral Oncológico Clara Campal (CIOCC), Madrid, 28050, Spain

Summary:
The goal of this First-In-Human (FIH) Phase I/II trial is to establish the safety profile, determine the Recommended Phase II Dose (RP2D), explore the pharmacokinetic (PK) exposure and pharmacodynamic (PD) properties as well as assess the efficacy of STX-241, a mutant selective Central Nervous System (CNS)-penetrant fourth generation EGFR TKI, in participants with locally advanced or metastatic NSCLC that progressed during or following third generation EGFR TKI such as osimertinib due to C797X double acquired (secondary) mutations.

Primary Outcome Measures: Safety: Part 1 and Part 2: Safety: Incidence and severity of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs), according to NCI-CTCAE v5.0 criteria., Screening to Safety Follow-up (30 days post last dose)|Part 1 and Part 2: Tolerability: Incidence of TEAEs/SAEs leading to STX-241 dose reductions, interruptions or discontinuations., Screening to Safety Follow-up (30 days post last dose)|Part 1: Maximum Tolerated Dose (MTD): Incidence of Dose-Limiting Toxicities (DLTs), From first STX-241 intake until 28 days post first dose (28 days post first dose)|Part 1: Optimal Biologically Active Dose (OBD), From the first STX-241 intake up to 24 months|Part 2: Recommended Phase II Dose (RP2D) of STX-241, From the first STX-241 intake up to 24 months|Part 2: cORR (Confirmed Overall Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per investigator., Up to 24 months|Part 3: cORR (Confirmed Overall Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per Blinded Independent Central Review (BICR)., Up to 24 months
Secondary Outcome Measures: All Parts: PK exposure parameter: Maximum Plasma Concentration (Cmax), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Time To Maximum Plasma Concentration (Tmax), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Dosing Interval (AUC0-tau), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Terminal Elimination Half-Life (t½), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Apparent Clearance (CL/F), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Apparent Volume Of Distribution (Vz/F), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Peak Plasma Concentration (Cmax), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Area Under The Plasma Concentration versus Time Curve (AUC), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|All Parts: PK exposure parameter: Trough Plasma Concentration (Ctrough), Part 1 and Part 2: C1 Day 1, Day 2, Day 15; C2 Day 1; C3 Day 1; - each cycle is 28 days; Part 3: C1 Day 1; C2 Day 1; C3 Day 1; - each cycle is 28 days|Part 1 and Part 3: cORR by Investigator Review (IR) in accordance to RECIST version 1.1., Up to 24 months|All parts: DCR (Disease Control Rate) by IR in accordance to RECIST version 1.1., Up to 24 months|All parts: TTR (Time To Response) by IR in accordance to (RECIST version 1.1., Up to 24 months|All parts: DOR (Duration of Response) by IR in accordance to RECIST version 1.1., Up to 24 months|Part 3: DCR (Disease Control Rate) by BICR in accordance to RECIST version 1.1., Up to 24 months|Part 3: TTR (Time To Response) by BICR in accordance to (RECIST version 1.1., Up to 24 months|Part 3: DOR (Duration of Response) by BICR in accordance to RECIST version 1.1., Up to 24 months|Part 2 and Part 3: PFS (Progression-Free Survival) ( by IR in accordance to RECIST version 1.1., Up to 24 months|Part 3: PFS (Progression-Free Survival) by BICR in accordance to RECIST version 1.1., Up to 24 months|Part 2 and Part 3: Overall Survival, Up to 24 months|Part 3: Safety: Incidence and severity of TEAEs/SAEs, From screening to Safety Follow-up (30 days post last dose)|Part 3: Tolerability: TEAEs/SAEs leading to STX-241 dose reductions, interruptions or discontinuations., Screening to Safety Follow-up (30 days post last dose)