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 now · Phase 2

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

In brief

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.

Key facts

Study ID

NCT05967689

Run by

Taiho Oncology, Inc.

People needed

220

Starts

2023-07-31

Expected to finish

2028-12-31

Last updated by the study team

2026-06-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Written informed consent.
• ≥18 years of age (or meets the country's regulatory definition of legal adult age, whichever is greater.
• Pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria:
• Cohort A participants:
• 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.
• i. Permitted prior ex20ins therapies include: amivantamab, sunvozertinib (DZD9008), and BLU451. Other prior ex20ins--directed treatment may be discussed with the Sponsor for eligibility assessment.
• 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.
• Cohort B participants:
• 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.
• Cohort C participants:
• 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.
• Cohort D participants:
• 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).
• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
• 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.

You may not qualify if…

• Participant is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged to be scientifically or medically incompatible with this study.
• Has received any of the following within the specific time frame specified:
• Participant has received Zipalertinib (TAS6417/CLN081) at any time
• CNS radiotherapy (gamma knife radiotherapy is allowed) ≤ 12 weeks, thoracic radiotherapy ≤ 28 days, or other palliative radiation ≤ 14 days prior to the first dose of study
• Anticancer immunotherapy ≤28 days prior to the first dose of study treatment
• Major surgery (excluding placement of vascular access) ≤28 days prior to the first dose of study treatment.
• Any prior treatment with an EGFR exon20ins- targeted TKI
• Participants with leptomeningeal CNS disease.
• Have any unresolved toxicity of Grade ≥2 from previous anticancer treatment, except for Grade 2 alopecia or skin pigmentation. Participants with other chronic but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
• Past medical history of interstitial lung disease, treatment-related pneumonitis (any grade), or evidence of clinically active interstitial lung disease.
• Impaired cardiac function or clinically significant cardiac disease including any of the following:
• History of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification.
• Serious cardiac arrhythmias requiring treatment.
• Resting corrected QT interval (QTc) >470 msec using Fridericia's formula (QTcF).
• Is unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal absorption of zipalertinib (eg, inflammatory bowel disease, malabsorption syndrome, or prior gastric/bowel resection).
• History of another primary malignancy ≤2 years prior to the date of first dose of study treatment unless at least one of the following criteria are met:
• Adequately treated basal or squamous cell carcinoma of the skin
• Cancer in situ of the breast or cervix
• Participants with previously treated malignancy if all treatment for that malignancy was completed at least 2 years prior to first dose and no evidence of disease
• Participants with concurrent malignancy clinically stable and not requiring tumor-directed treatment
• Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is not controlled with treatment.
• History of Coronavirus disease 2019 (COVID-19) infection within 4 weeks prior to enrollment and/or has persistent clinically significant pulmonary symptoms related to prior COVID-19 infection.
• Active bleeding disorders.
• Known hypersensitivity to the ingredients in zipalertinib or any drugs similar in structure or class.
• Is pregnant, lactating, or planning to become pregnant.

Where it is running

• William Osler Health System - Brampton Civic Hospital — Brampton, Canada (enrolling)
• Sendai Kousei Hospital — Sendai, Miyagi, Japan (enrolling)
• Centre Leon Berard — Lyon, Auvergne-Rhône-Alpes, France (enrolling)
• CHU Caen Normandie — Caen, Basse-Normandie, France (enrolling)
• Centre Hospitalier Universitaire Limoges — Limoges, Limousin, France (enrolling)
• Joondalup Hospital Pharmacy — Joondalup, Western Australia, Australia (enrolling)
• Hôpital Nord de Marseille — Marseille, Provence-Alpes-Côte d'Azur Region, France (enrolling)
• Hopital Nord Laennec — Saint-Herblain, France (enrolling)
• Hopital Ambroise Pare — Boulogne-Billancourt, Île-de-France Region, France (enrolling)
• Institut Curie — Paris, Île-de-France Region, France (enrolling)
• Gesundheit Nordhessen Holding AG — Kassel, Hassen, Germany (enrolling)
• Uniklinik Dresden — Dresden, Germany (enrolling)
• UKGM Studienzentrale — Giessen, Germany (enrolling)
• Hopital Haut Leveque — Pessac, New Aquitaine, France (enrolling)
• Queen Mary Hospital — Pok Fu Lam, Hong Kong Island, Hong Kong (enrolling)
• Azienda Ospedaliero - Universitaria Careggi — Florence, Florence, Italy (enrolling)
• Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST — Meldola, Forli-Cesena, Italy (enrolling)
• Azienda Socio-Sanitaria Territoriale di Cremona — Cremona, Italy (enrolling)
• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele — Milan, Italy (enrolling)
• Azienda Ospedaliero-Universitaria di Parma — Parma, Italy (enrolling)
• Ospedale S. Maria delle Croci — Ravenna, Italy (enrolling)
• Aichi Cancer Center — Nagoya, Aichi-ken, Japan (enrolling)
• National Cancer Center Hospital East — Kashiwa-shi, Chiba, Japan (enrolling)
• NHO Kyushu Cancer Center — Fukuoka, Hukuoka, Japan (enrolling)
• Niigata Cancer Center Hospital — Niigata, Niigata, Japan (enrolling)

Full record on ClinicalTrials.gov

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