"Only licensed physicians may submit an email inquiry/question about Taiho's Zipalertinib Expanded Access Program via email (Zipalertinib@parexel.com). If you are a patient or caregiver, do not email Parexel or Taiho. Please talk to your physician. Do not share any patient Personally Identifiable Information with Parexel."

The objective of the study is to provide access to zipalertinib to patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations whose disease has progressed on or after platinum-based chemotherapy with or without amivantamab.

This is an open-label EAP treatment protocol of zipalertinib for the treatment of patients with advanced NSCLC with EGFR ex20ins mutations who have exhausted standard treatment options, are new to therapy with zipalertinib, and for whom therapy with zipalertinib is clinically indicated.

Patients will be enrolled through the MyAccess Programs Platform.

Inclusion Criteria:

1. Has provided written informed consent.
2. Has histologically confirmed, locally advanced, metastatic, or recurrent unresectable NSCLC with EGFR ex20ins mutations based on testing performed by a qualified (CLIA certified) laboratory.

4. Has measurable or nonmeasurable lesion(s). 5. Has progressed on or after platinum-based chemotherapy with or without amivantamab.

6. Has progressed on available standard therapy or is unable to tolerate such standard therapy.

7. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.

8. Has adequate organ function. 9. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test prior to administration of the first dose of zipalertinib.

10. Both males and females of reproductive potential must agree to use effective birth control during the program prior to the first dose of zipalertinib and for 1 week after the last dose of zipalertinib.

11. Is able to take medications orally (feeding tube is not permitted).

Exclusion Criteria:

1. Has a history and/or current evidence of any of the following:

   • 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:

     1. History of congestive heart failure Class III/IV according to the New York Heart Association Functional Classification
     2. Serious cardiac arrhythmias requiring treatment

   • Use of zipalertinib (TAS6417/CLN-081) at any time.

2. Has not recovered from side effects of the following prior therapies:

   • Have any unresolved toxicity of Grade ≥ 2 from previous anticancer treatment, except for Grade 2 alopecia or skin pigmentation. Patients with other chronic but stable Grade 2 toxicities may be allowed to enroll after agreement between the treatment physician and Sponsor.
   • Thoracic radiotherapy ≤ 28 days or palliative radiation (gamma knife radiotherapy is allowed) ≤ 14 days prior to the first dose of zipalertinib
   • Anticancer immunotherapy ≤ 28 days prior to the first dose of zipalertinib
   • Major surgery (excluding placement of vascular access) ≤ 28 days prior to the first dose of zipalertinib.

3. Has a serious illness or medical condition(s) that in the judgment of the treating physician would make the patient inappropriate for entry into this program.

4. Has a history of another primary malignancy whose natural history or treatment has the potential to interfere with the safety assessment of zipalertinib in the opinion of the treating physician.

5. Has known hypersensitivity to the ingredients in zipalertinib or any drugs similar in structure or class.

6. Is pregnant, lactating, or planning to become pregnant.