Brief 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 prostatea walnut-shaped gland in the male reproductive system that is responsible for producing semen - a bodily fluid that acts as a vessel for sperm transport during ejaculation cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs (mCRPC).
Intervention / Treatment
- 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 Dosethe amount of medication taken 1 QD
- Drug: JSB462 Dose 2 QD
- Drug: JSB462 QD
- Drug: Standard of Care (SoC)
Inclusion Criteria
- Participant is an adult man ≥ 18 years of age.
- Participant must have histologically and/or cytologically confirmed adenocarcinomacancer arising from mucus-producing glands in organs of the prostate without neuroendocrine or small cell features (current or prior biopsyremoval of a section of tissue to analyse for cancer cells of the prostate and/or metastatic site).
- Participant must have ≥ 1 metastatic lesion that is present on screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening/baseline CT, MRI, or bone scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities imagingtests that create detailed images of areas inside the body 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 chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells:
- 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