Health Trials

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)

ConditionProgressive Metastatic Castrate Resistant Prostate Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorNovartis Pharmaceuticals

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

Participant is an adult man ≥ 18 years of age.

Participant must have histologically and/or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell features (current or prior biopsy of the prostate and/or metastatic site).

Participant must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to start of treatment (Part 1a dose escalation) or randomization (Part 1b dose expansion and Part 2).

Participant must have progressive mCRPC.

Disqualifiers

Previous treatment with any PRC2 inhibitor, including but not limited to EZH2 inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.

Previous treatment with a protein degrader compound that targets the AR.

Known hypersensitivity or contraindication to any of the study treatment components or its excipients or to drugs of similar chemical classes.

Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Tulmimetostat DL1 QD

    Drug

    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

    Drug

    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

    Drug

    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

    Drug

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

  • Tulmimetostat RP2D QD

    Drug

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

  • JSB462 Dose 1 QD

    Drug

    JSB462 Dose 1 QD

  • JSB462 Dose 2 QD

    Drug

    JSB462 Dose 2 QD

  • JSB462 QD

    Drug

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

  • Standard of Care (SoC)

    Drug

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

Treatment groups

188 Participants
are divided into 10 treatment groups

10

Treatment groups

See each treatment group below.

Group A: Part 1a: Cohort DL1AExperimental treatment 2 interventions
Group B: Part 1a: Cohort DL1BExperimental treatment 2 interventions
Group C: Part 1a: Cohort DL2AExperimental treatment 2 interventions
Group D: Part 1a: Cohort DL2BExperimental treatment 2 interventions
Group E: Part 1a: Cohort DL3AExperimental treatment 2 interventions
Group F: Part 1a: Cohort DL3BExperimental treatment 2 interventions
Group G: Part 1b : Arm AExperimental treatment 2 interventions
Group H: Part 1b: Arm BExperimental treatment 2 interventions
Group I: Part 2: Arm 1Experimental treatment 2 interventions
Group J: Part 2: Arm 2Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

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).

Time frame
Up to 28 days
2

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.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 14 months
3

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.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 14 months
4

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

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

Secondary outcomes

1

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

Time frame
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.
2

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

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

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.

Time frame
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.
4

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.

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

Other outcomes

Sponsors and contacts

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Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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