A Phase 1/2 Dose Escalation Trial With Administration Schedule Exploration Evaluating Single Agent TD001, a PSMA-Targeted Antibody-Drug Conjugate, in Patients With PSMA-Expressing Metastatic Castration-Resistant Prostate Cancer
Summary
This study will evaluate the safety, tolerability, drug levels (pharmacokinetics) and preliminary antitumor activity of TD001, an antibody-drug conjugate (ADC) targeting prostate-specific membrane antigen (PSMA), in men with metastatic PSMA-expressing castration-resistant prostate cancer (CRPC).
Detailed description
This is a first-in-human, open-label, multicenter Phase 1/2 study with a dose escalation part to determine recommended Phase 2 doses (RP2Ds) of TD001 for further evaluation in an expansion part of the study. Multiple dosing schedules may be evaluated. The safety and preliminary efficacy endpoints of this study will support dose optimization in this patient population.
Arms & interventions
- DrugTD001
Intravenous (IV) infusion at protocol-defined doses and schedules until disease progression or other reason to end treatment
Outcome measures
Primary
Maximum tolerated dose (dose escalation)
Number of participants with dose-limiting toxicity; incidence of adverse events (AEs), serious AEs (SAEs), abnormal laboratory parameters, TD001 discontinuation or modification due to AEs, as assessed by CTCAE v6.0
Time frame: Treatment + follow-up (estimated 9 months)
Recommended Phase 2 doses (dose escalation)
Incidence of AEs, SAEs, abnormal laboratory parameters, TD001 discontinuation or modification due to AEs, as assessed by CTCAE v6.0
Time frame: Treatment + follow-up (estimated 9 months)
Safety/tolerability - incidence of AEs, SAEs, abnormal laboratory parameters (dose escalation + expansion)
AEs, SAEs, abnormal laboratory parameters by type, severity, and relatedness as assessed by CTCAE v6.0
Time frame: Treatment + follow-up (estimated 21 months)
Safety/tolerability - incidence of TD001 discontinuation or modification due to AEs (dose escalation + expansion)
AEs by type, severity, and relatedness as assessed by CTCAE v6.0
Time frame: Treatment + follow-up (estimated 21 months)
Secondary
Plasma PK - AUC
Time frame: Estimated 6-8 months
Plasma PK - AUClast
Time frame: Estimated 6-8 months
Plasma PK - AUCtau
Time frame: Estimated 6-8 months
Plasma PK - Cmax
Time frame: Estimated 6-8 months
Plasma PK - Tmax
Time frame: Estimated 6-8 months
Plasma PK - T1/2
Time frame: Estimated 6-8 months
Plasma PK - Ctrough
Time frame: Estimated 6-8 months
PSA50 response rate
Time frame: Treatment (estimated 8 months)
Overall response rate
Time frame: Treatment (estimated 8 months)
PSA progression-free survival
Time frame: Treatment + follow-up (estimated 21 months)
Radiographic progression-free survival
Time frame: Treatment + follow-up (estimated 21 months)
Duration of response
Time frame: Treatment + follow-up (estimated 21 months)
Disease control rate
Time frame: Treatment (estimated 8 months)
Overall survival
Time frame: Treatment + follow-up (estimated 21 months)
Immunogenicity - prevalance and incidence of ADAs
Time frame: Treatment period + follow-up (estimated 9 months)
Eligibility criteria
Study locations (1)
Yale University, Yale Cancer Center
New Haven, Connecticut, 06520