Study of XNW5004 Tablet in Combination With Enzalutamide in Subjects With Metastatic Castration-Resistant Prostate Cancer

NCT06702995 | Recruiting Phase 1 FDA Drug

• 1 other identifier: XNW5004-Ib/II-01
• Study Type: interventional
• Target: 307
• Locations: 1 country
• Sites: 2

Brief Summary

In this phase Ib/II study, participants with metastatic castration-resistant prostate cancer (mCRPC) who failed prior novel hormone therapy will be treated with XNW5004 in combination with enzalutamide.

Conditions

Metastatic Castrate-Resistant Prostate Cancer; mCRPC (Metastatic Castration-resistant Prostate Cancer)

Keywords

XNW5004; Enzalutamide

Outcome Measures

Primary Outcomes (3)

• Ph Ib/IIa: Overall safety profile including adverse events

  Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[5.0\])

  Baseline up to approximately 2 years

• Ph Ib/IIa: Recommended phase 2 doses (RP2D) of XNW5004 in combination with enzalutamide

  RP2D of XNW5004 as administered orally twice daily (BID), continuously in 28-day cycles, in combination with enzalutamide in subjects with mCRPC by safety data, pharmacokinetic data, pharmacodynamic data and efficacy data

  Approximately 6 months

• Preliminary efficacy determination as evaluated by disease specific response criteria

  Radiographic Progression-free survival（rPFS）was defined as the time from the date of first administration of the study drug to the date of radiographic progression base on the investigator assessment per PCWG3 criteria or death due to any cause (whichever comes first) in Phase IIa/IIb.

  Baseline until disease progression or death or through study completion (approximately 2 years)

Secondary Outcomes (12)

• Ph Ib/IIa: Pharmacokinetic Parameters

  The first 28-day cycle of therapy

• Ph Ib/IIa: Pharmacokinetic Parameters

  The first 28-day cycle of therapy

• Ph Ib/IIa: Pharmacokinetic Parameters

  The first 28-day cycle of therapy

• Ph Ib/IIa: Pharmacokinetic Parameters

  The first 28-day cycle of therapy

• Ph Ib: Pharmacodynamic Parameters

  The first 28-day cycle of therapy

Study Arms (3)

Phase Ib

EXPERIMENTAL

Participants with mCRPC will receive XNW5004 at escalating dose levels in combination with enzalutamide.

Drug: XNW5004; Drug: enzalutamide

Phase IIa

EXPERIMENTAL

Participants with mCRPC will receive XNW5004 in combination with enzalutamide.

Drug: XNW5004; Drug: enzalutamide

Phase IIb

EXPERIMENTAL

Participants with mCRPC will receive XNW5004 in combination with enzalutamide or enzalutamide alone

Drug: XNW5004; Drug: enzalutamide

Interventions

XNW5004 DRUG

Oral continuous

Also known as: EZH2i

Phase IIa; Phase IIb; Phase Ib

enzalutamide DRUG

enzalutamide 160 mg (four 40 mg capsules) orally once daily

Also known as: Xtandi

Phase IIa; Phase IIb; Phase Ib

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have the ability to understand and sign an approved informed consent form (ICF).
• Age at the time of consent ≥ 18 years;
• Life expectancy of ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1;
• Prostate adenocarcinoma confirmed by histological or cytological examination, except neuroendocrine carcinoma or small cell carcinoma;
• Metastatic prostate cancer disease, documented by CT/MRI imaging/bone scan ;
• Ongoing luteinizing hormone-releasing hormone agonist (LHRHa) or antagonist therapy (medical castration) or prior bilateral orchiectomy (surgical castration); subjects who have not undergone bilateral orchiectomy must be scheduled for Maintain effective LHRHa therapy throughout the study period;
• Testosterone at castration level (≤50ng/dL or 1.7nmol/L) at screening;
• Progressive disease in the setting of medical or surgical castration for study entry, the subject has 1 or more of the following 3 items: (1) PSA progression, defined as PSA \> 1ng/ml and at least 2 episodes of PSA level elevation ≥ 1 week apart; (2) disease progression as defined by RECIST 1.1; (3) bone disease progression as defined by PCWG3 criteria, i.e., ≥ more than 2 new lesions found on bone scan;
• Previous anti-tumor therapy meet the following conditions： Ib and IIb: Failure of previous abiraterone acetate therapy (refers to disease progression during abiraterone acetate treatment; disease progression is defined as the same as in Article 9 of the enrollment criteria), and no next generation androgen receptor inhibitors (enzalutamide or apalutamide, etc.) have been used; IIb: Failure of previous only one approved novel hormone therapy, such as abiraterone acetate, apalutamide, darolutamide and rezvilutamide, etc., except enzalutamide；
• Adequate hematologic and non-hematologic function during the screening.
• Must agree to take adequate contraceptive measures from the beginning of the study to at least 3 months after the last dose of the test drug, and prohibit sperm donation;
• Ability to comply with all procedures of the clinical trial protocol.

You may not qualify if:

• Previous anti-tumor therapy meet the following conditions： Ib and IIb: previously received any next generation androgen receptor antagonists (such as enzalutamide, apalutamide, proxalutamide and rezvilutamide, etc.) ； IIa: previously received with enzalutamide or more than 1 novel hormone therapy;
• Prior chemotherapy for castration resistant disease (including but not limited to ADCs);
• Prior exposure to EZH2 inhibitor(s) (including but not limited to tazemetostat and EZH1/2 inhibitors);
• Subjects who received anti-tumor therapies including chemotherapy, immunotherapy, radical radiotherapy, major surgery, targeting therapy and other anti-tumor therapies within 4 weeks or 5 half-lives of the drug (whichever is shorter) before the first dose; or received palliative radiotherapy within 2 weeks before the first dose;
• Plan to receive any other anti-tumor therapy during this trial;
• Subjects who participated in any other clinical trial of anti-tumor therapy within 28 days before the first dosing, and the last dose of other anti-tumor trial drug is within 28 days prior to the first administration of study drug in this trial;
• Central nervous system metastasis or disease;
• Severe bone injury caused by tumor bone metastasis judged by the investigator, including severe bone pain with poor control, pathological fractures of important sites and spinal cord compression that occurred in the past 6 months or are expected to occur in the near future, etc.;
• Subjects who experienced stroke or other serious cerebrovascular diseases within 12 months prior to enrollment;
• Subjects who have impaired heart functions or clinically serious heart disease；
• Have severe systemic active infection;
• Have a history of tuberculosis within 1 year before enrollment, or had an active TB infection more than 1 year before but not received adequate anti-TB treatment;
• Subjects known to be allergic to the study drug or its active ingredients or excipients;
• Subjects taking known moderate or strong inducers and inhibitors of CYP3A within 14 days before the first administration;
• Active autoimmune and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic therapy, rheumatoid arthritis, inflammatory bowel disease, and Hashimoto's thyroiditis, etc., except type I diabetes, Hypothyroidism that can be controlled by replacement therapy alone, hyperthyroidism that is stable under drug control, skin diseases that do not require systemic therapy (eg, vitiligo, psoriasis);

Sponsors & Collaborators

• Evopoint Biosciences Inc.: lead

Study Sites (2)

Cancer Hosipital of Shandong First Medical University,440 Jiyan Road, Jinan City, Shandong Province

Jinan, Shandong, 250117, China

RECRUITING

270 Dongan Road, Shanghai

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

enzalutamide

Study Officials

• D Ye, M.D.

  Dingwei Ye

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junjie Zhang

CONTACT

86+15010250838; junjie.zhang@evopointbio.com

Qianqian Zhang

CONTACT

86+13552698575; qian1.zhang@evopointbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 25, 2024
• Study Start: April 19, 2023
• Primary Completion (Estimated): May 13, 2026
• Study Completion (Estimated): July 19, 2026
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)