Phase 1, Dose-Escalation Study of KTX2001 (an NSD2 Inhibitor) Alone and in Combination With Darolutamide for Metastatic Castration-Resistant Prostate Cancer
Study K36-MCRPC-001 is the first in human clinical trial testing KTX-2001 alone and with darolutamide in men with metastatic castration-resistant prostate cancer. The study aims to assess whether the drug is safe, increasing doses alone and in combination with darolutamide, whether it is effective in treating metastatic castration-resistant prostate cancer, and measuring how the drug(s) behaves in the body.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
• Male participants with mCRPC as defined by PCWG3 criteria.
• Metastatic disease documented using bone scan for bone metastases (PCWG3 criteria) or by computed tomography (CT) or magnetic resonance imaging (MRI) for soft-tissue metastases. Evidence of metastasis on prostate-specific membrane antigen positron emission tomography alone will not be sufficient for confirmation of metastatic disease.
• Willingness to undergo a baseline and on-treatment biopsy of a metastatic site if safe and feasible. If tissue from a biopsy of a metastatic site (including bone) obtained within the previous 6 months (prior to treatment start) is available, this tissue may be used, and the baseline biopsy may be omitted.
• Participants should have progressed on or after receiving an ARPI (eg, abiraterone, enzalutamide, darolutamide, or apalutamide).
• Adequate renal function (creatinine clearance \>50 mL/min by serum creatinine).
• Adequate hepatic function (total bilirubin ≤1.5× ULN, total bilirubin \<3× ULN for participants with documented Gilbert's syndrome, AST and ALT ≤2.5× ULN). In case of liver metastases, AST and ALT \<5× ULN is allowed.
• Adequate hematological function (neutrophils \>1 × 109/L, platelet count \>100 × 109/L, hemoglobin \>9 g/dL) with no prior transfusions within 2 weeks.