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

You may be able to join if

• A patient must meet ALL the following inclusion criteria to be eligible for enrollment to this study: Provide written informed consent
• 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.
• Is ≥18 years of age (or meets the country’s regulatory definition of legal adult age, whichever is greater)
• Has pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria: a.Cohort A patients: i. Documented EGFR ex20ins status, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US). ii. 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. Patients who discontinued previous treatment due to unacceptable toxicity are eligible. Permitted prior ex20ins therapies include: amivantamab, sunvozertinib (DZD9008), and BLU451. Other prior ex20ins-directed treatment may be discussed with the Sponsor for eligibility assessment. iii. Patients with brain metastasis must be neurologically stable. Patients 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. 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. Patients with a history of uncontrolled seizures or LMD are not eligible. b.Cohort B patients: i. Documented EGFR ex20 instatus, as determined by local testing performed at a CLIA certified (US) or locally certified laboratory (outside the US). c. Patients 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. iii. Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible.
• Has pathologically confirmed, locally advanced or metastatic NSCLC meeting all the following criteria: c.Cohort C patients: i. 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). ii. Presence of brain metastasis(es), characterized as at least one of the following: a. Newly diagnosed and/or progressive brain metastasis (es) measurable by RANO-BM criteria and not subjected to CNS-directed therapy, AND/OR b. Leptomeningeal disease (LMD) measurable by RANO-BM criteria and confirmed by a positive cerebrospinal fluid cytology, or unequivocal radiographic and/or clinical determination. iii. Patients 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. d.Cohort D patients: i. 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. ii. Patients with brain metastasis must be neurologically stable. Patients 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. Patients with history of uncontrolled seizures or leptomeningeal disease are not eligible. iii. Patients who have not received prior systemic therapy for their locally advanced or metastatic NSCLC disease. iv. Prior adjuvant/neoadjuvant treatment for early-stage disease must have been completed >6 months prior to the first dose of study treatment. Patients may not have received prior adjuvant/neoadjuvant treatment with any EGFR TKI.
• Measurable disease per RECIST 1.1.