Metastatic Castration-Resistant Prostatic Cancer
Conditions
Keywords
CRPC, PSMA, prostate-specific membrane antigen
Brief 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.
Interventions
DRUGTD001
Intravenous (IV) infusion at protocol-defined doses and schedules until disease progression or other reason to end treatment
Sponsors
T.O.A.D. Oncology SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3 + 3 dose escalation design followed by RP2D cohort expansion
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must fully understand the study requirements and voluntarily sign informed consent. * PSMA-expressing metastatic CRPC with documented progression based on serum PSA, RECIST 1.1 with PCWG3, and/or bone disease. * At least one measurable metastatic lesion per RECIST 1.1. * Adequate organ function. * Prior orchiectomy and/or ongoing androgen deprivation therapy. * Prior treatment with at least one androgen receptor pathway inhibitor (ARPI) drug.
Exclusion criteria
* Previous treatment with strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, or hemi-body irradiation, within 6 months before treatment. * Systemic anticancer therapy including an investigational agent within 28 days before treatment. * Known hypersensitivity to the components of TD001, its analogs, or excipients. * Current dyspnea at rest, other disease requiring continuous oxygen therapy, or history of pneumonitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (dose escalation) | Treatment + follow-up (estimated 9 months) | 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 |
| Recommended Phase 2 doses (dose escalation) | Treatment + follow-up (estimated 9 months) | Incidence of AEs, SAEs, abnormal laboratory parameters, TD001 discontinuation or modification due to AEs, as assessed by CTCAE v6.0 |
| Safety/tolerability - incidence of AEs, SAEs, abnormal laboratory parameters (dose escalation + expansion) | Treatment + follow-up (estimated 21 months) | AEs, SAEs, abnormal laboratory parameters by type, severity, and relatedness as assessed by CTCAE v6.0 |
| Safety/tolerability - incidence of TD001 discontinuation or modification due to AEs (dose escalation + expansion) | Treatment + follow-up (estimated 21 months) | AEs by type, severity, and relatedness as assessed by CTCAE v6.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK - AUC | Estimated 6-8 months | Area under the concentration-time curve for total ADC, total antibody, and unconjugated payload |
| Plasma PK - AUClast | Estimated 6-8 months | Area under concentration-time curve from time zero to the last measurable concentration for total ADC, total antibody, and unconjugated payload |
| Plasma PK - AUCtau | Estimated 6-8 months | Area under concentration-time curve from time zero to the end of the dosing interval for total ADC, total antibody, and unconjugated payload |
| Plasma PK - Cmax | Estimated 6-8 months | Maximum concentration for total ADC, total antibody, and unconjugated payload |
| Plasma PK - Tmax | Estimated 6-8 months | Time to maximum concentration for total ADC, total antibody, and unconjugated payload |
| Plasma PK - T1/2 | Estimated 6-8 months | Terminal elimination half-life for total ADC, total antibody, and unconjugated payload |
| Plasma PK - Ctrough | Estimated 6-8 months | Trough concentration for total ADC, total antibody, and unconjugated payload |
| PSA50 response rate | Treatment (estimated 8 months) | ≥50% PSA decrease from baseline, per PCWG3 |
| Overall response rate | Treatment (estimated 8 months) | Best response of CR or PR per PCWG3-modified RECIST 1.1 |
| PSA progression-free survival | Treatment + follow-up (estimated 21 months) | Per PCWG3 |
| Radiographic progression-free survival | Treatment + follow-up (estimated 21 months) | per PCWG3-modified RECIST 1.1 |
| Duration of response | Treatment + follow-up (estimated 21 months) | For PSA and radiographic response |
| Disease control rate | Treatment (estimated 8 months) | Best response of CR, PR or SD |
| Overall survival | Treatment + follow-up (estimated 21 months) | — |
| Immunogenicity - prevalance and incidence of ADAs | Treatment period + follow-up (estimated 9 months) | ADAs against TD001 prior to first dose and at any time on treatment |
Countries
Australia, Canada, France, Spain, United States
Contacts
CONTACTTOAD Clinical Operations
Outcome results
None listed