A First-In-Human (FIH) Phase I/II Open-label, Multicentre, Dose Escalation and Expansion Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors Including Non-small Cell Lung Cancer (NSCLC) Harboring Mesenchymal-Epithelial Transition (MET) Alterations
Summary
The goal of this clinical trial is to investigate the safety, the activity of VERT-002 (PFL-002), and the optimal safe dose to be used, in participants with solid tumors including non-small cell lung cancer.
Arms & interventions
- DrugVERT-002
Route of Administration: Intravenous
Outcome measures
Primary
Safety: All parts: Incidence and severity of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs), according to NCI-CTCAE v5.0 criteria.
Time frame: Screening to Safety Follow-up (30 days post last dose)
Tolerability: All parts: Incidence of TEAEs/SAEs leading to VERT-002 dose reduction, interruption or discontinuation.
Time frame: From screening up to 13 months
Part 1: Maximum Tolerated Dose (MTD): Incidence of Dose-Limiting Toxicities (DLTs)
Time frame: From the start of trial treatment until end of Cycle 1 per dose level
Part 1: Optimal Biologically Active Dose (OBD): Incidence on PK/PD and ORR (Objective Response Rate)
Time frame: From the first VERT-002 intake up to 13 months
Part2a: Preliminary activity assessment: ORR and cORR (Confirmed Objective Response Rate)
Time frame: From the start of trial treatment up to 13 months
Part2b: Recommended Phase 2 Dose (RP2D): Incidence on overall safety, PK, PDs and cORR
Time frame: From the start of trial treatment up to 13 months
Secondary
Serum PK Parameter: Maximum Plasma Concentration (Cmax)
Time frame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
Serum PK Parameter: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Dosing Interval (AUC0-tau)
Time frame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
Serum PK Parameter: Accumulation Ratio (Rac) for Maximum Observed Concentration (Cmax) and Area Under The Concentration-Time Curve (AUC)
Time frame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
Serum PK Parameter: Trough Concentration (Ctrough)
Time frame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
Serum ADA Parameter: Incidence of VERT-002 anti- drug antibodies (ADA)
Time frame: Parts 1 and 2: Cycle 1 Days 1,8, and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 8 months). Each cycle is 28 Days
All Parts: cORR (Confirmed Objective Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per Investigator's Reviewer (IR)
Time frame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
All Parts: DCR (Disease Control Rate) based on RECIST version 1.1 per IR
Time frame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
All Parts: TTR (Time To Response) according to RECIST version 1.1 per IR
Time frame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
All Parts: Duration Of Response (DOR) according to RECIST v1.1 per IR
Time frame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
Part 2: Progression Free Survival (PFS) according to RECIST v1.1 per IR
Time frame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
Part 2: Overall Survival (OS)
Time frame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
Eligibility criteria
Study locations (3)
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
Gabrail Cancer Research Center
Canton, Ohio, 44718
Sarah Cannon Research Institute Oncology Partners
Nashville, Tennessee, 37203