A Study of Zipalertinib for Advanced Non-Small Cell Lung Cancer with EGFR Exon 20 Insertions
This study is testing a drug called zipalertinib in people with advanced non-small cell lung cancer (NSCLC) that has specific changes in the EGFR gene, called exon 20 insertions or other uncommon mutations. Researchers want to see how safe and effective zipalertinib is. You might be able to join if you are 18 or older, have this type of lung cancer, and have either received prior treatment or are newly diagnosed and cannot have standard chemotherapy. The main goal is to see how many people respond to zipalertinib, meaning their cancer shrinks or stops growing. This will be measured for up to about two years. The study also looks at how zipalertinib interacts with other medications in your body. The current recruitment status is unclear, and the study plans to enroll 220 participants.
- Study design
- This is an interventional study with a planned enrollment of 220 participants. It includes different groups (cohorts) based on prior treatment.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The main outcomes will be measured for up to approximately two years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
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.
Recruiting
PHASE2Ages 18+InterventionalTreatmentTaiho Oncology, Inc.
~220 participants
Updated 2026-09-01 on ClinicalTrials.gov
What's tested:TAS6417CYP CocktailTransporter Cocktail
At a glance
Recruiting sites
70 of 80 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Cohorts 1-4: Objective Response Rate (ORR)
Measured over Up to approximately 2 years
+1 more outcome measured
Conditions
Where it's being run
80 sites across 47 statesSpain8
New York4
Italy4
Seoul Teugbyeolsi [Seoul-T'ukpyolshi]4
Turkey (Türkiye)4
England4
New Jersey3
Ohio3
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Documented EGFR ex20ins status, as determined by local testing performed at a Clinical Laboratory Improvement Amendments (CLIA) certified (United States \[US\]) or locally certified laboratory (outside the US).
Progressed on or after systemic therapy with an agent targeting ex20ins, either alone or in combination with standard platinum-based chemotherapy for the treatment of advanced disease. Participants who discontinued previous treatment due to unacceptable toxicity are eligible.
Participants with brain metastasis must be neurologically stable. Participants must have received central nervous system (CNS)-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\] scan) during the Screening Period. Additionally, they must be on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with a history of uncontrolled seizures or LMD are not eligible.
Documented EGFR ex20instatus, as determined by local testing performed at a CLIA-certified (US) or locally certified laboratory (outside the US).
Participants who have not received prior treatment for advanced or metastatic disease and who are not appropriate candidates for first-line doublet platinum-based chemotherapy based on Investigator judgment or has refused first-line doublet platinum-based chemotherapy following discussion with the Investigator. Prior adjuvant/neoadjuvant treatment for early-stage disease must have been completed \>6 months prior to the first dose of study treatment.
Participants with brain metastasis must be neurologically stable. Participants must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening Period, and they must be on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with history of uncontrolled seizures or LMD are not eligible.
Documented ex20ins or other uncommon single or compound EGFR non-ex20ins status, as determined by local testing performed at a CLIA-certified (US) or locally certified laboratory (outside the US).
Presence of brain metastasis(es) characterized as at least one of the following:
Newly diagnosed and/or progressive brain metastasis(es) measurable by Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) criteria and not subjected to CNS-directed therapy, AND/OR
LMD measurable or non-measurable by RANO-BM criteria and confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and/or clinical determination.
Participants may not require other immediate CNS-directed therapy or will likely require other CNS directed anti-tumor therapy during the first cycle of study treatment, as judged by the Investigator.
Documented other uncommon single or compound EGFR non-ex20ins status (excluding C797S), as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US). A list of eligible mutations will be provided in a separate document.
Participants with brain metastasis must be neurologically stable. Participants must have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS- directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the Screening Period, and they must be on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment. Participants with history of uncontrolled seizures or LMD are not eligible.
Participants who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease.
Prior adjuvant/neoadjuvant treatment for early-stage disease must have been completed \>6 months prior to the first dose of study treatment. Participants may not have received prior adjuvant/neoadjuvant treatment with any EGFR tyrosine kinase inhibitor (TKI). 4. Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). 5. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers (details provided in a laboratory manual). Participants with insufficient tissue may be eligible following discussion with the Sponsor. 6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 17. 7. Adequate organ function, as defined by the hematologic, renal and hepatic laboratory values. 8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of study treatment. Female participants are not considered to be of childbearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 9. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose of study drug and for 1 month after the last dose of study treatment.
ex20ins EGFRmt OR
other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) OR
common EGFRmt (eg, ex19del or L858R) 2. Participant has progressed on or after receiving prior standard of care (SoC) systemic therapy for their locally advanced or metastatic NSCLC disease unless:
Participant for whom no approved therapy with demonstrated clinical benefit is indicated or available,
Participant is intolerant to the available first-line (1L) SoC treatment options, OR
Participant has refused 1L SoC treatment options (after being appropriately informed of the treatment options, risks, and benefits). 3. Participants with brain metastasis are eligible if they fulfill all of the criteria below:
Have received CNS-directed therapy and have no evidence of progression for at least 4 weeks after CNS- directed treatment, as ascertained by brain imaging (MRI or CT scan) during the Screening Period,
Are on a stable or decreasing dose of corticosteroids and/or anti-convulsant medications for at least 2 weeks prior to the first dose of study treatment,
Are neurologically stable with no history of uncontrolled seizures. 4. ECOG PS of 0 or 1.
What this trial measures
- Cohorts 1-4: Objective Response Rate (ORR)Up to approximately 2 years
- Dose Optimization Substudy: ORR as Assessed by Blinded Independent Central Review (BICR)Up to approximately 2 years