LUXDEGALUTAMIDE for Metastatic castration-resistant prostate cancer (mCRPC)

Inclusion criteria

• {"criterion_text":"- Participant is an adult man ≥ 18 years of age.\n- 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).\n- 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).\n- Participant must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: •\tSerum/plasma PSA progression defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression •\tSoft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)] •\tProgression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016)).\n- Participant must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).\n- Prior ARPI therapy: •\tPart 1a and 1b only:must have progressed on at least one prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide). •\tPart 2 only:must have progressed on one prior second generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide).\n- Prior chemotherapy: •\tPart 1a dose escalation only: may have received ≤ 2 prior lines of chemotherapy in CRPC setting. Note: Prior chemotherapy is permitted in the HSPC setting. •\tPart 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. •\tPart 2 only: Participants must be taxane-naïve in mCRPC setting; prior chemotherapy permitted in HSPC setting only"}

Exclusion criteria

• {"criterion_text":"- Previous treatment with any PRC2 inhibitor, including but not limited to EZH2 inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.\n- Previous treatment with a protein degrader compound that targets the AR.\n- Known hypersensitivity or contraindication to any of the study treatment components or its excipients or to drugs of similar chemical classes.\n- Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.\n- Previous treatment with radioligand therapy in the mCRPC setting, except in Part 1a where participants may have received RLT in mCRPC setting.\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- •\tPart 1a: Dose-limiting toxicities (DLTs) •\tPart 1a and Part 1b: Safety: Type, frequency and severity of AEs per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and notable values in laboratory, vital signs, and electrocardiogram (ECGs). Tolerability: Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to each study drug","definition_or_measurement_approach":"DLTs assessed in Part 1a; Safety assessed by type, frequency and severity of AEs per CTCAE v5.0 and notable lab/vital sign/ECG values; Tolerability assessed by dose interruptions, reductions, discontinuations, dose intensity and duration of exposure."}
• {"endpoint_text":"- Part 1b and Part 2: PSA50 at Month 6, defined as the PSA reduction of at least 50% from baseline at 6 months confirmed by a second PSA measurement ≥ 3 weeks later.","definition_or_measurement_approach":"PSA50 at Month 6 defined as a ≥50% reduction in PSA from baseline at 6 months confirmed by a second PSA measurement ≥3 weeks later."}

Secondary endpoints

• {"endpoint_text":"- Plasma concentrations of tulmimetostat and JSB462 (Phase I and Phase II), and derived PK parameters including AUC and Cmax (Phase I only)","definition_or_measurement_approach":"Measurement of plasma concentrations and derived PK parameters (AUC, Cmax); PK sampling and analysis in Phase I (and concentrations in Phase II)."}
• {"endpoint_text":"- Radiographic progression free survival (rPFS) 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;","definition_or_measurement_approach":"rPFS defined as time from randomization to first disease progression per PCWG3-modified RECIST v1.1 or death from any cause."}
• {"endpoint_text":"- Overall survival (OS) is defined as the time between randomization to date of death due to any cause","definition_or_measurement_approach":"OS defined as time from randomization to date of death due to any cause."}
• {"endpoint_text":"- Objective response (OR) is defined as a confirmed complete response (CR) or partial response (PR) per PCWG3-modified RECIST 1.1 as assessed by the investigator","definition_or_measurement_approach":"OR defined as confirmed CR or PR per PCWG3-modified RECIST v1.1 assessed by investigator."}
• {"endpoint_text":"- Best overall response (BOR) is defined as the best response per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 as assessed by the Investigator","definition_or_measurement_approach":"BOR defined as best response per PCWG3-modified RECIST v1.1 as assessed by investigator."}
• {"endpoint_text":"- Duration of response (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","definition_or_measurement_approach":"DOR defined as time between first documented CR/PR and disease progression or death per PCWG3-modified RECIST v1.1."}
• {"endpoint_text":"- Part 1b and Part 2: Time to first symptomatic skeletal event (TTSSE ) 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.","definition_or_measurement_approach":"TTSSE defined as time from randomization to first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgery, need for radiation to relieve bone pain, or death, whichever occurs first."}
• {"endpoint_text":"- Safety: Type, frequency and severity of adverse events (AEs) per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and notable values in laboratory, vital signs, and ECGs.","definition_or_measurement_approach":"Safety assessed by type, frequency and severity of AEs per CTCAE v5.0 and notable lab/vital sign/ECG abnormalities."}
• {"endpoint_text":"- Tolerability: Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to each study drug","definition_or_measurement_approach":"Tolerability assessed by recording dose interruptions, reductions, discontinuations, dose intensity and exposure duration for each study drug."}
• {"endpoint_text":"- PSA50 at 3, 9 and 12 months, radiographic progression free survival (rPFS), overall survival (OS), objective response (OR), best overall response (BOR) and duration of response (DOR)","definition_or_measurement_approach":"PSA50 and other endpoints assessed at specified timepoints per definitions above (PSA50 = ≥50% reduction from baseline confirmed as specified; rPFS/OS/OR/BOR/DOR per PCWG3-modified RECIST definitions)."}

Denmark

Earliest CTIS Part Ii Submission Date

03-11-2025

Latest Decision Or Authorization Date

01-12-2025

Processing Time Days

28

Number Of Sites

3

Number Of Participants

14

France

Earliest CTIS Part Ii Submission Date

24-10-2025

Latest Decision Or Authorization Date

03-12-2025

Processing Time Days

40

Number Of Sites

6

Number Of Participants

17

Germany

Earliest CTIS Part Ii Submission Date

18-11-2025

Latest Decision Or Authorization Date

04-12-2025

Processing Time Days

16

Number Of Sites

2

Number Of Participants

13

Italy

Earliest CTIS Part Ii Submission Date

23-10-2025

Latest Decision Or Authorization Date

03-12-2025

Processing Time Days

41

Number Of Sites

3

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

24-10-2025

Latest Decision Or Authorization Date

09-12-2025

Processing Time Days

46

Number Of Sites

4

Number Of Participants

18

Poland

Earliest CTIS Part Ii Submission Date

04-09-2025

Latest Decision Or Authorization Date

08-12-2025

Processing Time Days

95

Number Of Sites

1

Number Of Participants

8

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: 13 (and additional role code: 1 in another entry)

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties code: 12

Name

IQVIA Limited

Responsibilities

sponsorDuties codes: 1, 13, 3

Name

Syneos Health Inc.

Responsibilities

sponsorDuties code: 1

Name

Navigate Biopharma Services Inc.

Responsibilities

sponsorDuties code: 4

Third parties

• {"country":"Italy","full_name":"Phardis S.r.l.","duties_or_roles":"Local Drug Supply","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"PRO management, PRO licensing, formatting and translations","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties code: 13","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO management, PRO licensing, formatting and translations","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited (additional role)","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 6, 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Saale-Apotheke Dr. Christian Wegner e.Kfm.","duties_or_roles":"Central Pharmacy","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1, 13, 3","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties code: 12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Bioservices","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}