NCT05967689

A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation.

An Open-Label, Phase 2b, Global Multicenter Cohort Trial to Assess the Safety and Efficacy of Zipalertinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Exon 20 Insertion and Uncommon/Single or Compound Epidermal Growth Factor Receptor Mutations.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 220 (estimated)
• Sponsor: Taiho Oncology, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of zipalertinib in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harboring EGFR ex20ins mutations and other mutations.

Detailed description

This study will evaluate the safety and efficacy of zipalertinib in participants with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations or other uncommon/single or compound Epidermal Growth Factor Receptor Proteins Mutations (EGFRmts). The drug-drug interaction (DDI) substudy will assess the potential DDI effects of zipalertinib on the pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme substrates and transporter substrates and also evaluate the relationship between zipalertinib concentration and QT interval change from baseline. Additionally, dose optimization substudy will be conducted to confirm an optimized dose of zipalertinib monotherapy. Participants will be enrolled into 1 of the 4 following cohorts: * Cohort A ("prior ex20ins treatment") will include participants harboring EGFR ex20ins who have progressed on or after initial treatment with standard platinum-based chemotherapy and prior treatment with an ex20ins agent for their advanced disease (administered together or separately). * Cohort B ("first-line") will include participants harboring EGFR ex20ins who have not received prior treatment for advanced or metastatic disease and are not appropriate candidates for first-line doublet platinum-based chemotherapy or have refused first-line doublet platinum-based chemotherapy. * Cohort C ("active brain mets") will include participants harboring EGFR ex20ins or other uncommon single or compound EGFRmts and active brain metastases and/or leptomeningeal disease (LMD). Participants may or may not have had prior treatment for advanced disease. * Cohort D ("other uncommon EGFRmts") will include participants harboring other non-ex20ins, excluding C797S (uncommon single or compound) EGFRmts who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease. For DDI substudy, participants will be enrolled in two groups: * CYP Cocktail Group will receive a single dose of cocktail of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state. * Transporter Cocktail Group will receive a single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state. For dose-optimization substudy, participants with locally advanced or metastatic NSCLC harboring epidermal growth factor receptor protein ex20ins mutations (EGFRmts) will be randomized to receive zipalertinib at different doses with continuous daily dosing until any discontinuation criterion is met. Participants will be enrolled into two groups: Arm A and Arm B, in which they will receive different doses of zipalertinib.

Conditions

• Advanced or Metastatic NSCLC Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion (ex20ins) Mutations

Interventions

Type	Name	Description
DRUG	TAS6417	Oral tablets
DRUG	CYP Cocktail	Single dose of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state.
DRUG	Transporter Cocktail	Single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state.

Timeline

• Start date: 2023-07-31
• Primary completion: 2028-08-31
• Completion: 2028-12-31
• First posted: 2023-08-01
• Last updated: 2026-04-03

Locations

80 sites across 12 countries: United States, Australia, Canada, France, Germany, Hong Kong, Italy, Japan, South Korea, Spain, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study