Study of TYK-01054 Capsules in Patients With Advanced Solid Tumors

NCT ID: NCT07282873

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2029-06-30

Brief Summary

This study is to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of the TEAD inhibitor TYK-01054 capsules in patients with locally advanced or metastatic advanced solid tumors

Detailed Description

Dose Escalation (Part A) will employ an accelerated titration design combined with a "3 + 3" design to evaluate the safety and pharmacokinetic (PK) profile of TYK-01054 in patients with mesothelioma and/or metastatic solid tumors who are resistant to standard therapy or for which no effective standard therapy is available. Dose escalation phase comprises a single-dose stage (7 days) and a continuous dosing stage. Accelerated titration will switch to the conventional 3+3 design as soon as any patient experiences a ≥Grade 2 TYK-01054-related toxicity or when the second patient at any dose level completes the first cycle without dose-limiting toxicity (DLT). Dose escalation will continue until the Maximum Tolerated Dose (MTD), Recommended Dose for Expansion (RDE), or a suitable intermittent dosing regimen is determined. The RDE(s) selected in Part A will be carried forward into the dose optimisation phase.

Dose Optimization (Part B) will further assess safety and PK, and will evaluate preliminary anti-tumor activity at two RDE levels. Approximately 40 patients with four target indications will be enrolled and randomised 1:1 to receive either RDE or RDE-1. Based on PK, safety, and all cumulative data, the Study Review Committee (SRC) will determine the dose for the Part c (i.e., the Recommended Phase 2 Dose, RP2D).

Cohort Expansion (Part C) includes four cohorts.

• Cohort 1: Advanced (unresectable or metastatic) malignant mesothelioma(MM); regardless of NF2 mutation status or other Hippo pathway abnormalities.
• Cohort 2: Advanced (unresectable or metastatic) Small-cell lung cancer (SCLC) that has progressed after first-line therapy.
• Cohort 3: Advanced (unresectable or metastatic) Head-and-neck squamous-cell carcinoma (HNSCC) that has progressed after first-line systemic therapy.
• Cohort 4: Advanced (unresectable or metastatic) solid tumours; priority will be given to colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), non-small-cell lung cancer (NSCLC), and epithelioid haemangioendothelioma (EHE).

Cohorts 2-4 require that patients also have abnormalities in the Hippo signaling pathway, NF2, MST1/2, LATS1/2, FAT1 mutations/alterations or YAP/TAZ fusion.

Conditions

Solid Tumor Malignancies; Malignant Mesothelioma (MM)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TKY-01054

TKY-01054，orally administered daily

Group Type: EXPERIMENTAL

TYK-01054

Intervention Type: DRUG

TKY-01054 will be administered orally at a starting dose of 25 mg in 21-day cycles. If well tolerated, dose expansion will proceed in the recommended dose for expansion (RDE) and RDE-1 until the recommended Phase II dose (RP2D) is determined.

Interventions

TYK-01054

TKY-01054 will be administered orally at a starting dose of 25 mg in 21-day cycles. If well tolerated, dose expansion will proceed in the recommended dose for expansion (RDE) and RDE-1 until the recommended Phase II dose (RP2D) is determined.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female subjects ≥18 years old

2. Histologically or cytologically confirmed incurable, locally advanced or metastatic advanced solid tumors. All participants are required to provide results of Hippo signaling pathway gene testing; however, this requirement is not a mandatory inclusion criterion for Dose Escalation (Part A) and EHE patients.

3. Advanced solid tumors must have progressed after receiving at least one standard first-line anti-tumor therapy, OR demonstrate intolerance to standard therapy, OR Lack of standard treatment.

4. Patients should have at least 1 measurable lesion as per RECIST v1.1 or mRECIST v1.1.

5. Adequate organ function, including hepatic, renal, cardiovascular, astrointestinal,respiratory, and hematopoietic systems.

6. ECOG 0-1，

7. Life expectancy of >3 months.

8. Willing and able to comply with all aspects of the protocol.

Exclusion Criteria

1. History of other malignancy, except for:

Non-melanoma skin cancer (basal cell carcinoma or squamous cell carcinoma) that is non-invasive and has been effectively controlled with no recurrence or metastasis for 5 years, Papillary thyroid carcinoma, Carcinoma in situ of the cervix, Ductal carcinoma in situ of the breast.

2. Unstable brain metastases,such as:

Patients requiring urgent neurosurgical intervention for CNS complications, Presence of symptomatic spinal cord compression due to tumor, Presence of leptomeningeal disease (carcinomatous meningitis).

3. Presence of pleural effusion, pericardial effusion, or ascites that, in the investigator's judgment, cannot be stably controlled by repeated drainage or other methods.

4. Clinically significant renal disease.

5. Clinically significant cardiovascular disease, including but not limited to myocardial infarction, unstable angina, congestive heart failure (NYHA Class ≥ II), or uncontrolled arrhythmias.

6. Patients with uncontrolled infectious diseases, such as immunodeficiency disorders (e.g., HIV) or active hepatitis B or C infection; chronic hepatitis B or C carriers without symptoms are excluded from this criterion.

7. Known or suspected hypersensitivity to TYK-01054 or any of its excipients, or to compounds of similar chemical class.

8. Patients who have previously received a TEAD inhibitor.

9. Women who are pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TYK Medicines, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Facility Contacts

Shun Lu, MD

Role: primary

Other Identifiers

TYKM1408101

Identifier Type: -

Identifier Source: org_study_id