This is a phase Ia/Ib, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of BC3195 in subjects with locally advanced or metastatic solid tumors in whom standard treatment has failed (either due to disease progression or intolerance). This study will consist of two parts: Dose escalation (Part 1) and dose expansion (Part 2). Each part will include a screening period, a treatment period, and follow-up period.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
148
BC3195 is a novel antibody drug conjugate (ADC) targeting CDH3 (calcium-dependent adhesion 3). The payload, monomethyl auristatin E (MMAE), is a microtubule disrupting agent covalently attached to the antibody via a cleavable dipeptide linker Val-Cit (vc).
Case Western Reserve University
Cleveland, Ohio, United States
RECRUITINGIncidence of Dose Limiting Toxicities (DLTs)
Time frame: First 21 days of treatment
Determination of the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
Time frame: Day 1 of treatment through 30 days after the last dose
Incidence and Severity of All Adverse Events (AEs)
Time frame: Screening through 12 weeks after the last dose
Objective Response Rate (ORR)
Assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
Time frame: Day 1 of treatment through 6 weeks after the last dose
Disease Control Rate (DCR)
Proportion of subjects with CR, PR, and stable disease (SD)
Time frame: Day 1 of treatment through 6 weeks after the last dose
Duration of Response (DoR)
Defined as the time from the date when the measurement criteria were met for complete or partial response (whichever occurred first) until the date of the first observed PD or death of any cause
Time frame: Day 1 of treatment through 6 weeks after the last dose
Time to Progression (TTP)
Defined as the length of time from the start of treatment until first evidence of disease progression
Time frame: Day 1 of treatment through 6 weeks after the last dose
Progression Free Survival (PFS)
Defined as the time from which the subject is enrolled to the date of any recorded disease progression or the death of any cause
Time frame: Day 1 of treatment through 6 weeks after the last dose
Overall Survival (OS)
Defined as the time from Day 1 of dosing until the date of death from any cause assessed up to 100 months
Time frame: Patient consent until death Day 1 of dosing until the date of death from any cause assessed up to 100 months
Area under the curve (AUC) of BC3195
Area under the BC3195 time vs concentration curve
Time frame: Day 1 of dosing through 21 days post last dose
Maximum concentration (Cmax) of BC3195
Maximum concentration observed following dosing
Time frame: Day 1 of dosing through 21 days post last dose
Time to reach maximum concentration (Tmax) of BC3195
Time at which the maximum concentration of BC3195 is observed
Time frame: Day 1 of dosing through 21 days post last dose
Half-life (t 1/2) of BC3195
Time at which BC3195 concentration is reduced by one half
Time frame: Day 1 of dosing through 21 days post last dose
Volume of distribution (Vd) of BC3195
Volume of distribution
Time frame: Day 1 of dosing through 21 days post last dose
Clearance (CL) of BC3195
Volume of drug cleared in a period of time
Time frame: Day 1 of dosing through 21 days post last dose
Immunogenicity indicators
Anti-drug antibody (ADA)
Time frame: Day 1 of dosing through 30 days post last dose
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