Study of TYK-00540 Combined With Enzalutamide in Patients With Metastatic Castration-resistant Prostate Cancer（mCRPC）

NCT07104643 | Not Yet Recruiting Phase 1

• 1 other identifier: TYKM5807201
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the safety, and preliminary antitumor activity of TYK-00540 combined with Enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) that have failed novel endocrine therapy

Conditions

mCRPC

Outcome Measures

Primary Outcomes (5)

• Number of participants who experience one or more adverse events (AEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  From Baseline up to 28 days after the end of the treatment

• Dose Limiting Toxicity (DLT)

  Numbers of participants experiencing AEs which are defined as DLTs classfied by CTCAE v5.0.

  Up to approximately 28 days

• Maximum tolerated dose（MTD）

  To determine the maximum tolerated dose for combination-agent escalation.

  Within 28 days of the first dose

• Recommended Phase 2 Dose（RP2D）

  The RP2D is defined as the dose level chosen for the dose expansion arms, based on safety, tolerability, efficacy collected during the dose escalation portion of the study

  Within 28 days of the last patient dosed in escalation stage

• Progression-free survival (rPFS）

  rPFS is defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 is ≥20% increase in the sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria is the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for ≥6 weeks.

  Up to approximately 21 months

Secondary Outcomes (4)

• Prostate-specific antigen (PSA) response rate

  Up to approximately 21 months

• Overall survival (OS)

  Up to approximately 21 months

• Duration of response (DOR)

  Up to approximately 21 months

• Objective response rate (ORR)

  Up to approximately 21 months

Study Arms (1)

TYK-00540+Enzalutamide

EXPERIMENTAL

Find the maximum tolerated dose(MTD) and the recommended phase 2 dose (RP2D) of TYK-00540, given orally. • Increased dose cohorts from low dose to MTD, starting at 20mg twice a day. Enzalutamide, 160mg each time, once a day.

Drug: TYK-00540; Drug: Enzalutamide

Interventions

TYK-00540 DRUG

Take the specified dose (20mg or 30mg) orally twice a day. Take it on an empty stomach in the morning with about 200 mL of warm water.

TYK-00540+Enzalutamide

Enzalutamide DRUG

Take orally, 160mg each time, once a day. Take orally with or without meals.

TYK-00540+Enzalutamide

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Metastatic castration-resistant prostate adenocarcinoma confirmed by pathology (with no neuroendocrine or small cell features indicated by the initial pathological examination), if pathological examination is performed in the subsequent CRPC stage, the accompanying other pathological types should not exceed 10%. Those with only pelvic lymph node metastasis or local recurrence and metastasis (such as in the bladder, rectum, etc.) cannot be included.
• At the time of screening, testosterone levels were at castration levels (≤50ng/dL or 1.70nmol/L). If the patient had not previously undergone bilateral orchiectomy, they must be undergoing and voluntarily continue to receive LHRH agonists/antagonists for androgen deprivation therapy throughout the study treatment period.
• During screening, if the disease progresses, that is, the subject experiences one or more of the following three conditions; PSA progression is defined as no PSA \> 1ng/ml and at least two elevated PSA levels with an interval of ≥1 week. ② Disease progression as defined in RECIST 1.1; ③ Bone disease progression as defined by the PCWG3 standard refers to the discovery of ≥2 new lesions on bone scans.
• ECOG score ≤1, no deterioration in the two weeks prior to study enrollment, and an expected survival period of ≥3 months
• Have good organ functions, including:
• Liver function Total bilirubin (TBIL) ≤ 1.5×ULN (except for documented Gilbert syndrome), alanine aminotransferase (ALT) ≤ 2.5×ULN, and aspartate aminotransferase (AST) ≤ 2.5×ULN (for patients with liver metastasis, ALT/AST≤5×ULN), albumin ≥3.0g/L;
• Renal function enhancement: Serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance rate ≥50 mL/min;
• \<S:1\> Blood routine: PLT ≥ 100×109/L, ANC ≥ 1.5×109/L, WBC≥ 3.5×109/L and Hb ≥ 90g/L;
• The international normalized ratio (INR) is ≤1.5, and the activated partial prothrombin time (APTT) is ≤1.5×ULN;
• The patient agrees to maintain abstinence (control heterosexual sexual intercourse) or take contraceptive measures, and agrees not to donate sperm;
• Understand and voluntarily sign the written ICF, and have the willingness and ability to complete regular visits, treatment plans, laboratory tests and other experimental processes.

You may not qualify if:

• Subjects with the following treatments:
• Those who have previously received selective CDK2, CDK4 inhibitors, CDK4/6 inhibitors (e.g., Palbociclib, Ribociclib, Abemaciclib, Trilaciclib/G1T38, SHR6390, pirociclib) for treatment;
• Previously received enzalutamide or two or more novel endocrine therapies for prostate cancer;
• Isotope therapy with strontium-89, samarium or radium-223 was received within 12 weeks prior to the first administration;
• Systemic treatment for prostate cancer (anti-androgen therapy, chemotherapy, targeted therapy, immunotherapy, or other interventional clinical trial drugs, except castration therapy drugs) has been received within 4 weeks prior to the first medication.
• Systemic treatment for prostate cancer (anti-androgen therapy, chemotherapy, targeted therapy, immunotherapy, or other interventional clinical trial drugs, except castration therapy drugs) has been received within 4 weeks prior to the first medication.
• The patient has received blood transfusion, albumin infusion or used hematopoietic growth factor within 2 weeks before the first administration;
• Major surgery was performed within 28 days before the first administration of the drug , or surgery was performed when the surgical effect had not yet recovered at the time of screening or during the planned enrollment for treatment;
• Has received allogeneic transplants such as stem cell transplantation, bone marrow transplantation or liver transplantation in the past;
• Palliative radiotherapy was received within 2 weeks before the first administration;
• The first administration was within no more than five half-lives from the implantation of radioactive particles;
• The first administration was within no more than five half-lives from the implantation of radioactive particles.
• In addition to prostate cancer, there are other malignant tumors at the same time (excluding basal cell carcinoma or squamous cell carcinoma of the skin that can be treated locally and have been cured, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma of the breast and papillary thyroid carcinoma, etc.); Excluding those with other malignant tumors who have been cured of radical treatment for ≥5 years;
• In addition to prostate cancer, there are other malignant tumors at the same time (excluding basal cell carcinoma or squamous cell carcinoma of the skin that can be treated locally and have been cured, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma of the breast and papillary thyroid carcinoma, etc.); Excluding those with other malignant tumors who have been cured of radical treatment for ≥5 years;
• Known to be allergic to any excipients of TYK-00540 tablets, or allergic to enzalutamide and its excipients;

Sponsors & Collaborators

• TYK Medicines, Inc: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Interventions

enzalutamide

Study Officials

• Ji Zhu, Doctor of Medicine

  Doctor of Medicine

  PRINCIPAL INVESTIGATOR

• Doctor of Medicine

  Zhejiang Cancer Hospital, Hangzhou, zhejiang

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ji Zhu, Doctor of Medicine

CONTACT

0571-88122222; zhuji@zjcc.org.cn

Yan Sun, Doctor of Medicine

CONTACT

13735818864; sunyan592@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 5, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)