Study of TYK-00540 Tablets in Patients With Advanced Solid Tumors

NCT06950086 | Recruiting Phase 1

• 1 other identifier: TYKM5807101
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

This study is to evaluate the safety, pharmacokinetics, and preliminary antitumor activity of TYK-00540 as monotherapy or combined with fulvestrant in advanced solid tumors.

Conditions

HR-positive, HER2-negative Advanced Breast Cancer

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity (DLT)

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

  Within 31 days of the first dose

• Recommended dose for combination-agent escalation and single-agent expansion (RDE)

  To determine the recommended dose for combination-agent escalation and single-agent expansion agent expansion.

  1 year

• Adverse events (AEs)

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

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

• Objective response rate (ORR)

  ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  At least 24 weeks

Secondary Outcomes (4)

• The time to the peak concentration (Tmax)

  0 hours (h) (within 30 min before dosing), 0.25 h, 0.5 h , 1 h , 2 h , 3 h, 4 h, 8 h , 12 h, 24 h after dosing

• Maximum plasma concentration (Cmax)

  0 hours (h) (within 30 min before dosing), 0.25 h, 0.5 h , 1 h , 2 h , 3 h, 4 h, 8 h , 12 h, 24 h after dosing

• Minimum plasma concentration (Cmin)

  0 hours (h) (within 30 min before dosing), 0.25 h, 0.5 h , 1 h , 2 h , 3 h, 4 h, 8 h , 12 h, 24 h after dosing

• Disease Control Rate (DCR)

  At least 24 weeks

Study Arms (1)

TYK-00540±Fulvestrant

EXPERIMENTAL

TYK-00540• 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 5mg twicely. fulvestrant: is in the form of a syringe containing 5ml of an injection solution of 250mg of fulvestrant for injection. The recommended dose is every 28 days, once at a dose of 500mg, and on the 15th day after the initial injection, a loading dose of fulvestrant 500mg id added.

Drug: TYK-00540

Interventions

TYK-00540 DRUG

Increased dose cohorts from low to MTD (5mg Cohort 1;10 mg Cohort 2; 20 mg Cohort 3; 30 mg Cohort 4;40 mg Cohort 5) decreased dose cohorts for the combination (TYK-00540 30 mg+Fulvestrant Cohort 1;TYK-00540 20mg +Fulvestrant)

TYK-00540±Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years, gender requirements:
• Monotherapy dose-escalation phase: No gender restriction.
• Combination dose-selection phase: No gender restriction.
• Monotherapy and combination expansion phases:
• Cohort A-1: Females only.
• Other cohorts: No gender restriction.
• Monotherapy Dose-Escalation Phase:
• Histologically or cytologically confirmed locally advanced/metastatic solid tumors with no standard treatment available, failure of/intolerance to standard treatment, or refusal of standard treatment.
• Monotherapy Dose-Expansion Phase:
• Cohort A-1: Histologically or cytologically confirmed advanced platinum-resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer:
• Platinum resistance defined as: Disease recurrence/progression \<6 months after completion of prior platinum-based chemotherapy (≥4 cycles) or progression during initial/recurrent treatment.
• Disease recurrence/progression requires:
• Objective radiographic progression; OR
• Persistent CA125 elevation (confirmed after 1 week) with clinical symptoms or signs of progression.
• prior lines of chemotherapy for recurrent/metastatic disease, with ≤1 systemic therapy after platinum resistance.

You may not qualify if:

• Known hypersensitivity to any excipient of TYK-00540 or contraindication to fulvestrant (for Combination Dose-Selection and Combination Expansion Phases).
• Prior/concurrent therapies:
• Systemic anticancer therapies within 28 days prior to first dose: chemotherapy, large-molecule targeted therapy, immunotherapy.
• Endocrine therapy, small-molecule targeted therapy, or fluorouracil-based oral agents within 14 days prior to first dose.
• Nitrosoureas or mitomycin within 6 weeks prior to first dose. Anticancer herbal medicine or traditional Chinese medicine within 7 days prior to first dose.
• Local radiotherapy (e.g., thoracic/rib) or palliative radiotherapy for bone metastases within 7 days prior to first dose.
• Major surgery (excluding minor procedures, e.g., appendectomy, tumor biopsy) within 4 weeks prior to first dose.
• Proton pump inhibitor (PPI) use within 7 days prior to first dose or during the study.
• Concurrent use of medications known to prolong QTc interval or induce torsades de pointes (Appendix V).
• Participation in other interventional clinical trials within 28 days prior to first dose (non-interventional trials excluded).
• Prior allogeneic bone marrow transplantation. For Combination Phases: prior use of fulvestrant, other SERDs, or SERCAs.
• History of other malignancies, except:Cured basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, thyroid papillary carcinoma, ductal carcinoma in situ of the breast, or malignancies with disease-free survival \>3 years.
• Residual toxicity from prior therapy \>Grade 1 (except alopecia or platinum-related neuropathy).
• Central nervous system (CNS) disease:Primary CNS tumors, CNS metastases with prior local treatment failure, or newly diagnosed CNS metastases.Exception: Asymptomatic, stable CNS metastases (no steroids/CNS-specific treatment ≥14 days, radiologically confirmed stability at screening).
• Spinal cord compression caused by tumor.

Sponsors & Collaborators

• TYK Medicines, Inc: lead

Study Sites (2)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

Central Study Contacts

Jian Zhang

CONTACT

021-64175590; syner2000@163.com

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: April 11, 2025
• First Posted: April 29, 2025
• Study Start: January 2, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)