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)

Condition(s) studied

Investigational drug(s) / intervention(s)

Tulmimetostat DL1 QD: Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))

Tulmimetostat DL2 QD: Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))

Tulmimetostat DL3 QD: Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s))

Tulmimetostat Doses 1 or 2 QD: Part 1b (dose expansion and optimization): tulmimetostat doses 1 or 2 QD

Tulmimetostat RP2D QD: Part 2: tulmimetostat Recommended Phase 2 Dose (RP2D) QD

JSB462 Dose 1 QD: JSB462 Dose 1 QD

JSB462 Dose 2 QD: JSB462 Dose 2 QD

JSB462 QD: The dose of JSB462 QD will be determined based on the totality of data from Part 1a

Standard of Care (SoC): Androgen Receptor Pathway Inhibitors (ARPI), chemotherapy or Pluvicto (AAA617) at the discretion of the investigator

Study summary

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).

Eligibility

Primary outcome measure(s)

• Part 1a: Dose-limiting toxicities (DLTs) — Up to 28 days
  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).
• Part 1a and Part 1b: Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) — From date of randomization till 30 days safety fup, assessed up to approximately 14 months
  The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
• Part 1a and Part 1b: Number of Participants with dose adjustments — From date of randomization till 30 days safety fup, assessed up to approximately 14 months
  The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
• Part 1a and Part 1b: Dose Intensity — From date of randomization till 30 days safety fup, assessed up to approximately 14 months
  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
• Part 1a and Part 1b: Duration of exposure to each study drug — From date of randomization till 30 days safety fup, assessed up to approximately 14 months
  The duration of exposure (in months) to Tulmimetostat and JSB462 (Part 1a and Part 1b) will be summarized by means of descriptive statistics
• Part 1b and Part 2: prostate-specific antigen 50 (PSA50) at Month 6 — 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.

Trial sites (35)

More Novartis Pharmaceuticals trials in the UK