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)
Purpose
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).
Condition
- Progressive Metastatic Castrate Resistant Prostate Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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. - Participant must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L). - Prior ARPI therapy: - Part 1a and 1b only: must have progressed on at least one prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). - Part 2 only: must have progressed on one prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). - Prior chemotherapy: - Part 1a dose escalation only: may have received ≤ 2 prior lines of chemotherapy in CRPC setting. Note: Prior chemotherapy is permitted in the HSPC setting. - Part 1b dose expansion/optimization only: may have received up to one prior line of chemotherapy in CRPC setting. Note: Prior chemotherapy is permitted in the HSPC setting. - Part 2 only: Participants must be taxane-naïve in mCRPC setting; prior chemotherapy permitted in HSPC setting only
Exclusion Criteria
- 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. - Previous treatment with radioligand therapy in the mCRPC setting, except in Part 1a where participants may have received RLT in mCRPC setting. - Participants with evidence of mCRPC or biochemical recurrence / PSA only disease or asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy and with normal PSA for ≥ 1 year prior to study entry. - Participants with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purpose of maintaining neurologic integrity. Those with leptomeningeal disease are eligible if those areas have been treated, are stable, and no neurological impairment is present. For those with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain with MRI (preferred) or CT with contrast. Other protocol-defined inclusion/exclusion criteria may apply.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Part 1a (dose escalation): Participants will be assigned to cohorts to receive study treatment (tulmimetostat and JSB462) at different provisional dose levels. Part 1b (dose expansion and optimization): Participants will be randomized in a ratio and receive study treatment as: - Arm A: Tulmimetostat Dose 1 QD + JSB462 QD - Arm B: Tulmimetostat Dose 2 QD + JSB462 QD Part 2: Participants will be randomized in a ratio and receive study treatment as: - Arm 1: Tulmimetostat RP2D QD + JSB462 (either Dose 1 or Dose 2 QD) - Arm 2 (Control): SoC (ARPI, chemotherapy, Pluvicto) at the discretion of the investigator
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1a: Cohort DL1A |
Tulmimetostat DL1 QD + JSB462 Dose 1 QD |
|
|
Experimental Part 1a: Cohort DL1B |
Tulmimetostat DL1 QD + JSB462 Dose 2 QD |
|
|
Experimental Part 1a: Cohort DL2A |
Tulmimetostat DL2 QD + JSB462 Dose 1 QD |
|
|
Experimental Part 1a: Cohort DL2B |
Tulmimetostat DL2 QD + JSB462 Dose 2 QD |
|
|
Experimental Part 1a: Cohort DL3A |
Tulmimetostat DL3 QD + JSB462 Dose 1 QD |
|
|
Experimental Part 1a: Cohort DL3B |
Tulmimetostat DL3 QD + JSB462 Dose 2 QD |
|
|
Experimental Part 1b : Arm A |
Tulmimetostat Dose 1 QD + JSB462 QD |
|
|
Experimental Part 1b: Arm B |
Tulmimetostat Dose 2 QD + JSB462 QD |
|
|
Experimental Part 2: Arm 1 |
Tulmimetostat RP2D QD + JSB462 QD |
|
|
Active Comparator Part 2: Arm 2 |
Standard of Care at the discretion of the investigator |
|
Recruiting Locations
Sarah Cannon Research Institute
Denver 5419384, Colorado 5417618 80218
Denver 5419384, Colorado 5417618 80218
Sarah Cannon Research Institute
Jacksonville 4160021, Florida 4155751 32256
Jacksonville 4160021, Florida 4155751 32256
Wichita Urology Group PA
Wichita 4281730, Kansas 4273857 67226
Wichita 4281730, Kansas 4273857 67226
Fred Hutchinson Cancer Research Center
Seattle 5809844, Washington 5815135 98109-1024
Seattle 5809844, Washington 5815135 98109-1024
More Details
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
Detailed Description
The Phase 1 study, comprised of Parts 1a and 1b, aims to assess the safety and tolerability of the combination of tulmimetostat and JSB462: 1. Part 1a is the parallel dose escalation that aims to determine the recommended dose(s) of tulmimetostat and JSB462, in combination, for further exploration. 2. Part 1b is the dose expansion/optimization that aims to determine the recommended dose of the combination for Phase II. The purpose of the Phase II study (Part 2) is to compare the combination of tulmimetostat with JSB462 in terms of the biochemical response as assessed by PSA50 compared to the standard of care (SoC) in adult men with progressive, taxane-naive mCRPC.