An Open-label Dose Escalation and Expansion, Followed by a Phase II Study of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC) (TulmiSTAR-01)

Sintesi

This is a two-part, Phase I/II, open-label, global, multicenter study assessing the safety and efficacy of the combination of tulmimetostat (DZR123) and JSB462 (luxdegalutamide) versus standard of care in participants with progressive metastatic castrate resistant prostate cancer (mCRPC).

Idoneità

Disegno dello studio

Esiti misurati

1. Esito primario

   Part 1a: Dose-limiting toxicities (DLTs)

   A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the first 28 days of treatment with tulmimetostat and JSB462 and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose-escalation decisions, DLTs will be considered and included in the Bayesian Logistic Regression Model (BLRM).

   Orizzonte temporale Up to 28 days

2. Esito primario

   Part 1a and Part 1b: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)

   The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.

   Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 14 months

3. Esito primario

   Part 1a and Part 1b: Number of Participants with dose adjustments

   The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.

   Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 14 months

4. Esito primario

   Part 1a and Part 1b: Dose Intensity

   Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics

   Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 14 months

5. Esito primario

   Part 1a and Part 1b: Duration of exposure to each study drug

   The duration of exposure (in months) to Tulmimetostat and JSB462 (Part 1a and Part 1b) will be summarized by means of descriptive statistics

   Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 14 months

6. Esito primario

   Part 1b and Part 2: prostate-specific antigen 50 (PSA50) at Month 6

   PSA50 is defined as a PSA reduction of at least 50% from baseline at 6 months confirmed by a second PSA measurement ≥ 3 weeks later.

   Orizzonte temporale Month 6

7. Esito secondario

   Part 1a and Part 1b: Plasma concentrations of tulmimetostat and JSB462

   Tulmimetostat and JSB462 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels by treatment arms

   Orizzonte temporale Cycle 1-2: Day 1 (predose/0 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours; Tulmimetostat only: 30 minutes and 3 hours). Cycle 1: Day 2 (24 hours), Days 8 and 15 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.

8. Esito secondario

   Part 2: Plasma concentrations of tulmimetostat and JSB462

   Tulmimetostat and JSB462 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels by treatment arms

   Orizzonte temporale Cycle 1 and 2: Day 1 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.

9. Esito secondario

   Part 1a and Part 1b: AUC of tulmimetostat and JSB462

   Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) and Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) will be listed and summarized using descriptive statistics.

   Orizzonte temporale Cycle 1-2: Day 1 (predose/0 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours; Tulmimetostat only: 30 minutes and 3 hours). Cycle 1: Day 2 (24 hours), Days 8 and 15 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.

10. Esito secondario

    Part 2: AUC of tulmimetostat and JSB462

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) and Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) will be listed and summarized using descriptive statistics.

    Orizzonte temporale Cycle 1 and 2: Day 1 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.

11. Esito secondario

    Part 1a and Part 1b: Cmax of tulmimetostat and JSB462

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

    Orizzonte temporale Cycle 1-2: Day 1 (predose/0 hour, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours; Tulmimetostat only: 30 minutes and 3 hours). Cycle 1: Day 2 (24 hours), Days 8 and 15 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.

12. Esito secondario

    Part 2: Cmax of tulmimetostat and JSB462

    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

    Orizzonte temporale Cycle 1 and 2: Day 1 (predose/0 hour and 2 hours). Cycles 3-5: Day 1 (predose/0 hour). 1 cycle = 28 days.

13. Esito secondario

    Part 1b and Part 2: prostate-specific antigen 50 (PSA50) at 3, 9, and 12 months

    PSA50 is defined as a PSA reduction of at least 50% from baseline at 3, 9, and 12 months confirmed by a second PSA measurement ≥ 3 weeks later.

    Orizzonte temporale Month 3, Month 9, Month 12

14. Esito secondario

    Part 1b and Part 2: radiographic progression free survival (rPFS)

    rPFS is defined as time between randomization and the first occurrence of disease progression as per PCWG3-modified RECIST v1.1 or death due to any cause

    Orizzonte temporale From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months

15. Esito secondario

    Part 1b and Part 2: overall survival (OS)

    OS is defined as the time between randomization to date of death due to any cause

    Orizzonte temporale From date of randomization until date of death from any cause, assessed up to approximately 15 months

16. Esito secondario

    Part 1b and Part 2: objective response (OR)

    OR is defined as a confirmed complete response (CR) or partial response (PR) per PCWG3-modified RECIST 1.1 as assessed by the investigator

    Orizzonte temporale From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 15 months

17. Esito secondario

    Part 1b and Part 2: best overall response (BOR)

    BOR is defined as the best response per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 as assessed by the Investigator

    Orizzonte temporale From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 15 months

18. Esito secondario

    Part 1b and Part 2: duration of response (DOR)

    DOR is defined as time between first documented CR/PR and disease progression or death due to any cause per PCWG3-modified RECIST 1.1 as assessed by the investigator

    Orizzonte temporale From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 15 months

19. Esito secondario

    Part 1b and Part 2: time to first symptomatic skeletal event (TTSSE)

    TTSSE is defined as time from randomization to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first.

    Orizzonte temporale From randomization until the first occurrence of a new symptomatic bone fracture, spinal cord compression, tumor-related orthopedic surgery, radiation therapy for bone pain, or death, assessed up to 15 months.

20. Esito secondario

    Part 2: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.

    Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 15 months

21. Esito secondario

    Part 2: Number of Participants with dose adjustments

    The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.

    Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 15 months

22. Esito secondario

    Part 2: Dose Intensity

    Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics

    Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 15 months

23. Esito secondario

    Part 2: Duration of exposure to each study drug

    The duration of exposure (in months) to Tulmimetostat and JSB462 / Standard of Care (SoC) of investigator's choice (Part 2) will be summarized within each strata by means of descriptive statistics

    Orizzonte temporale From date of randomization till 30 days safety fup, assessed up to approximately 15 months

Date

«Effettiva» significa che l'evento è avvenuto. «Stimata» significa che lo sponsor lo prevede. Le due cose non sono equivalenti.

Centri

35 centri stanno reclutando

Documenti dello studio

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Modifiche nel tempo

1. 21 agosto 2026

   Centro aggiunto

   1 site added (35 total)

   34 → 35

2. 18 agosto 2026

   Centro aggiunto

   1 site added (34 total)

   33 → 34