Title
Phase 1, Dose-Escalation Study of KTX2001 (an NSD2 Inhibitor) Alone and in Combination With Darolutamide for Metastatic Castration-Resistant Prostate Cancer

Description
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.

Objective
Primary
- Part A: Investigate the safety and tolerability of KTX-2001 in participants
with mCRPC and determine the MTD/highest exposure dose and schedule for KTX-2001 as a single agent.
- Part B: Investigate the safety and tolerability of KTX-2001+darolutamide in
participants with mCRPC.
- Determine the RP2D of KTX-2001 based on data from Part A and Part B.

Secondary
- Characterize PK parameters of KTX-2001 when administered as single agent or in
combination with darolutamide.
- Part A: Provide preliminary efficacy data on the antitumor effects of KTX-2001.
- Part B: Provide preliminary efficacy data on the antitumor effects of KTX-2001+darolutamide

Treatment Study K36-MCRPC-001 (also know as K36-STRIKE-001) is a multicenter, open-label Phase 1 study for participants with metastatic castration-resistant prostate cancer (mCRPC) to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of KTX-2001 monotherapy and KTX-2001 in combination with darolutamide (NUBEQA®), and to establish a recommended Phase 2 dose(s) of KTX-2001 for future study.

Key Eligibility Inclusion Criteria:

-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 -Adequate hematological function (neutrophils >1 × 109/L, platelet count >100 × 109/L, hemoglobin >9 g/dL) with no prior transfusions within 2 weeks.

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital