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NCT07206056PHASE1, PHASE2Recruiting

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)

Novartis Pharmaceuticals

Start Date

10/15/2025

Completion Date

12/1/2030

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).

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Key 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 Key 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.

Interventions

DRUG

Tulmimetostat DL1 QD

DRUG

Tulmimetostat DL2 QD

DRUG

Tulmimetostat DL3 QD

DRUG

Tulmimetostat Doses 1 or 2 QD

DRUG

Tulmimetostat RP2D QD

DRUG

JSB462 Dose 1 QD

DRUG

JSB462 Dose 2 QD

DRUG

JSB462 QD

DRUG

Standard of Care (SoC)

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Conditions

Progressive Metastatic Castrate Resistant Prostate Cancer

Locations

Sarah Cannon Research Institute

Denver, Colorado 80218

United States

Sarah Cannon Research Institute

Jacksonville, Florida 32256

United States

Emory University

Atlanta, Georgia 30329

United States

Wichita Urology Group PA

Wichita, Kansas 67226

United States

Mass General Hospital

Boston, Massachusetts 02114

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109-1024

United States

Novartis Investigative Site

St Leonards, New South Wales 2065

Australia

Novartis Investigative Site

Melbourne, Victoria 3000

Australia

Novartis Investigative Site

Liverpool, 2170

Australia

Novartis Investigative Site

Halifax, Nova Scotia B3H 2Y9

Canada

Novartis Investigative Site

Beijing, 100021

China

Novartis Investigative Site

Herlev, DK-2730

Denmark

Novartis Investigative Site

Odense C, 5000

Denmark

Novartis Investigative Site

Vejle, DK-7100

Denmark

Novartis Investigative Site

Bordeaux, 33076

France

Novartis Investigative Site

Paris, 75015

France

Novartis Investigative Site

Paris, 75231

France

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia 40225

Germany

Novartis Investigative Site

Milan, MI 20133

Italy

Novartis Investigative Site

Padova, PD 35128

Italy

Novartis Investigative Site

Orbassano, TO 10043

Italy

Novartis Investigative Site

Kuching, Sarawak 93586

Malaysia

Novartis Investigative Site

Tlalpan, Mexico City 14050

Mexico

Novartis Investigative Site

Poznan, 60-192

Poland

Novartis Investigative Site

Singapore, 119074

Singapore

Novartis Investigative Site

Singapore, S308433

Singapore

Novartis Investigative Site

Santiago Compostela, A Coruna 15706

Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona 08907

Spain

Novartis Investigative Site

Madrid, 28009

Spain

Novartis Investigative Site

Madrid, 28041

Spain

Novartis Investigative Site

Sutton, Surrey SM2 5PT

United Kingdom

Novartis Investigative Site

London, W1G 6AD

United Kingdom