A clinical trial to learn about the effects of DZR123 and JSB462 given together in men with advanced prostate cancer that has stopped responding to other treatments

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Feb 2026 → ongoing

Decision date (initial)

2025-12-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG, OMS ID: ORG-100003908

External identifiers

EU CT number

2025-521880-10-00

WHO UTN

U1111-1325-8208

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Dose response, Others, Pharmacokinetic, Safety

Phase I
• Part 1a: To determine the recommended dose(s) for expansion (RDE) of tulmimetostat and JSB462 in combination
• Part 1a and Part 1b: To characterize the safety and tolerability of tulmimetostat in combination with JSB462
• Part 1b: To determine the recommended Phase II dose (RP2D) of tulmimetostat and JSB462 in combination
• Part 1b: To assess the biochemical response rate (BCR) as detected by PSA50 at Month 6 in participants treated with tulmimetostat and JSB462 at the RDEs
Phase II - Part 2
• To compare the BCR as assessed by PSA50 at Month 6 of the combination of tulmimetostat and JSB462 with the standard of care treatment (SoC)

Secondary objectives 8

1. Part 1a: To characterize the pharmacokinetic (PK) of tulmimetostat and JSB462 in combination
2. Part 1b: To characterize biochemical response rate (BCR) as assessed by 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) in participants treated with tulmimetostat and JSB462 at the recommended dose(s) for expansion (RDEs)
3. Part 1b: To further characterize the PK of tulmimetostat and JSB462 in combination
4. Part 1b: To evaluate the time to first symptomatic skeletal event (TTSSE)
5. Phase II – Part 2: To characterize the safety and tolerability profile in the treatment arms
6. Phase II – Part 2: To characterize BCR as assessed by PSA50 at 3, 9, and 12 months, rPFS, OS, OR, BOR, and DOR in participants treated with tulmimetostat in combination with JSB462 + ADT compared with SoC
7. Phase II – Part 2: To further characterize the PK of tulmimetostat and JSB462 in combination
8. Phase II – Part 2: To evaluate the TTSSE

Conditions and MedDRA coding

Metastatic castrate resistant prostate cancer (mCRPC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participant is an adult man ≥ 18 years of age.
2. 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).
3. 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).
4. Participant must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: • Serum/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 • Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)] • Progression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016))
5. Participant must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
6. 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).
7. 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 7

1. Previous treatment with any PRC2 inhibitor, including but not limited to EZH2 inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.
2. Previous treatment with a protein degrader compound that targets the AR.
3. Known hypersensitivity or contraindication to any of the study treatment components or its excipients or to drugs of similar chemical classes.
4. Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
5. Previous treatment with radioligand therapy in the mCRPC setting, except in Part 1a where participants may have received RLT in mCRPC setting.
6. 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.
7. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Part 1a: Dose-limiting toxicities (DLTs) • Part 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
2. 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.

Secondary endpoints 10

1. Plasma concentrations of tulmimetostat and JSB462 (Phase I and Phase II), and derived PK parameters including AUC and Cmax (Phase I only)
2. 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;
3. Overall survival (OS) is defined as the time between randomization to date of death due to any cause
4. 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
5. 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
6. 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
7. 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.
8. 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.
9. Tolerability: Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to each study drug
10. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 4

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 18

Locations

6 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications