NCT07282873

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

A Phase I/II, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of the TEAD Inhibitor TYK-01054 Capsules in Patients With Locally Advanced or Metastatic Advanced Solid Tumors

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 219 (estimated)
• Sponsor: TYK Medicines, Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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)

Interventions

Type	Name	Description
DRUG	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.

Timeline

• Start date: 2026-01-01
• Primary completion: 2028-01-01
• Completion: 2029-06-01
• First posted: 2025-12-15
• Last updated: 2025-12-22

Locations

1 site across 1 country: China