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

This Phase 1/2 trial evaluates TD001, a PSMA-targeted antibody-drug conjugate, in patients with PSMA-expressing metastatic castration-resistant prostate cancer. The primary objective in the dose escalation phase is to determine the maximum tolerated dose and recommended Phase 2 doses of TD001 across different administration schedules, while evaluating the safety and tolerability of these schedules. In the dose expansion phase, the primary objective is to evaluate the safety and tolerability of the recommended Phase 2 dose(s) of TD001 with the selected administration schedules. These objectives are clinically relevant for establishing the optimal dosing regimen and confirming the safety profile of this novel targeted therapeutic agent in this patient population.

The secondary objectives include:

• To characterize the pharmacokinetic and exposure-safety/response pharmacodynamic profiles of TD001
• To assess PSA response rate
• To assess preliminary antitumor activity of TD001 based on the radiographic response rate per PCWG3-modified RECIST 1.1
• To assess radiographic and biochemical progression-free survival per PCWG3-modified RECIST 1.1
• To characterize the immunogenicity of TD001

The clinical trial enrolled a total of **70 participants**, all of whom were **adult males** diagnosed with **metastatic castration-resistant prostate cancer** (mCRPC). The study population consisted of individuals aged 18 years and older, including both adults and elderly participants. Participants were required to demonstrate documented progressive mCRPC, evidenced by at least one of the following: serum **PSA** (prostate-specific antigen) progression, soft-tissue or visceral progression per RECIST 1.1 criteria with PCWG3 guidelines, or progression of bone disease according to PCWG3 criteria. Eligible participants had at least one measurable **metastatic lesion** per RECIST 1.1 and had undergone prior **orchiectomy** and/or were receiving ongoing **androgen deprivation therapy** (ADT). The selection criteria required that participants had received at least one **androgen receptor pathway inhibitor** and at least one but no more than two **taxane agents**, or were deemed unsuitable for such treatment. Additionally, participants with a **homologous recombination repair gene mutation** were required to have received a **PARP inhibitor** or be unsuitable for this treatment. The trial did not include vulnerable populations.

This is a **Phase 1/2** integrated clinical trial evaluating **TD001**, a **PSMA-targeted antibody-drug conjugate**, administered as a **solution for infusion** via the **intravenous route** in adult male patients with **PSMA-expressing metastatic castration-resistant prostate cancer**. The study employs a dose escalation design followed by dose expansion to determine the **maximum tolerated dose** and **recommended Phase 2 dose(s)** of TD001 across different administration schedules. The trial is designed to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of the investigational medicinal product in this patient population.

The dose escalation phase aims to determine the maximum tolerated dose and recommended Phase 2 dose(s) of TD001 administration schedules and to evaluate safety and tolerability. The dose expansion phase focuses on evaluating the safety and tolerability of the recommended Phase 2 dose(s) with specific administration schedules. Primary endpoints include the incidence and severity of **dose-limiting toxicities** during Cycle 1 in the dose escalation phase, incidence and severity of **adverse events** and **serious adverse events**, laboratory parameters, and treatment discontinuations or modifications due to adverse events. Secondary endpoints encompass pharmacokinetic parameters including **area under the curve**, **maximum concentration**, **time to maximum concentration**, **half-life**, and trough concentration of total antibody-drug conjugate, total antibody, and unconjugated exatecan payload, as well as efficacy measures such as **PSA50 response rate**, **objective response rate**, **PSA progression-free survival**, **radiographic progression-free survival**, duration of response, disease control rate, **overall survival**, and prevalence of **anti-drug antibodies** against TD001.

Eligible participants include adult males with documented progressive metastatic castration-resistant prostate cancer based on serum **PSA progression**, soft-tissue or visceral progression per **RECIST 1.1** with **PCWG3** criteria, or progression of bone disease according to PCWG3 criteria. Participants must have at least one measurable metastatic lesion per RECIST 1.1 and must have undergone prior **orchiectomy** and/or be receiving ongoing **androgen deprivation therapy**. Prior treatment requirements include at least one **androgen receptor pathway inhibitor** and at least one but no more than two taxane agents, or unsuitability for such treatment. Participants with **homologous recombination repair gene mutations** must have received a **PARP inhibitor** or be unsuitable for such treatment.

The trial is estimated to commence recruitment in January 2026 and is expected to conclude by December 2028, representing an overall trial duration of approximately three years. Participant involvement duration will vary depending on individual response to treatment, tolerability, and disease progression. Participants may be withdrawn from the study due to disease progression, unacceptable toxicity, withdrawal of consent, treatment modifications exceeding protocol-defined limits, or investigator decision based on participant safety considerations.

The experimental treatment under investigation in this clinical trial is **TD001**, a **PSMA-targeted antibody-drug conjugate**. TD001 is formulated as a **solution for infusion** and is administered via the **intravenous route**. The active substance in this medicinal product is TD001, which is classified as a protein of other origin. The study follows a Phase 1/2 dose escalation design with administration schedule exploration to determine the **maximum tolerated dose (MTD)** and **recommended Phase 2 dose (RP2D)** of various administration schedules. During the dose escalation phase, the primary objectives include establishing the MTD and RP2D of TD001 administration schedules, as well as evaluating the safety and tolerability of these schedules. The dose expansion phase aims to further evaluate the safety and tolerability of the established RP2D(s) with their respective administration schedules. The trial is conducted in patients with PSMA-expressing **metastatic castration-resistant prostate cancer**. Specific dosing amounts, frequency of administration, maximum daily dose, maximum total dose, and treatment duration are determined according to the dose escalation protocol design. Participant compliance monitoring and drug administration procedures follow standard clinical trial protocols for intravenous infusion therapies.

Efficacy will be assessed through multiple parameters in this clinical trial. The primary efficacy endpoints include the incidence and severity of dose-limiting toxicities during Cycle 1 in the dose escalation phase, the incidence, severity, and relationship of adverse events and serious adverse events, laboratory parameters, and treatment discontinuations and treatment modifications due to adverse events. Secondary efficacy endpoints encompass plasma concentration profile parameters including area under the curve, maximum concentration, time to maximum concentration, half-life, and trough concentration of total antibody-drug conjugate, total antibody, and unconjugated exatecan payload. Additional secondary endpoints include PSA50 response rate, objective response rate by investigator assessment, PSA progression-free survival, radiographic progression-free survival by investigator assessment, duration of response assessed through both PSA and radiographic measures by investigator assessment, disease control rate, overall survival, and the prevalence and plasma titers of anti-drug antibodies against TD001. The evaluation will utilize Response Evaluation Criteria in Solid Tumors version 1.1 with Prostate Cancer Working Group 3 criteria for assessment of soft-tissue, visceral, and bone disease progression.