The purpose of this study is to compare the efficacy of zipalertinib combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in participants with early stage (stage IB-IIIA) resected non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor mutation (EGFRmt).

DRUG: Cisplatin

IV infusion.

DRUG: Carboplatin

IV infusion.

DRUG: Pemetrexed

IV infusion.

DRUG: TAS6417

Oral tablets.

DRUG: Zipalertinib Matching-placebo

Oral tablets.

1. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
2. Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendment (CLIA) certified (United States [US]) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt:
   1. exon20 insertion mutations (ex20ins) or
   2. other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I)
3. Magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain done prior to surgery. Participants in whom this was not done prior to surgery may still be enrolled if appropriate imaging (i.e., MRI or CT of the brain) is performed prior to randomization.
4. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumor. Resection may be accomplished by open thoracotomy or video associated thoracic surgery (VATS) techniques.
5. Classified post-operatively as either Stage IB, IIA, IIB, or IIIA according to the tumor nodes metastasis (TNM) staging system for lung cancer (American Joint Committee on Cancer [AJCC] 9th edition).
6. Complete recovery from surgery at the time of randomization.
7. Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
8. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.

1. Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
2. Treatment with any of the following within the time frame specified:
   1. Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time.
   2. Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
   3. Any prior systemic anticancer therapy (e.g., neoadjuvant chemotherapy), including investigational therapy, for treatment of NSCLC.
   4. Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
   5. All prescribed medication, over-the-counter medication, vitamin preparations and other food supplements, or herbal medications that are strong or moderate cytochrome p450 (CYP) 3A4 inducers or inhibitors within 7 days prior to first dose.
   6. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
3. Has received only segmentectomies or wedge resections.
4. Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
5. Impaired cardiac function or clinically significant cardiac disease.
6. Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).
7. Participants with a history of any other cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, other cancers curatively treated with no evidence of disease for >5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment. Screening not required.
9. Active bleeding disorders.
10. Known:
    a. Hypersensitivity: i. To the ingredients in zipalertinib/placebo or any drugs similar in structure or class. ii. To platinum-containing drugs (i.e., cisplatin, carboplatin), pemetrexed, or any known excipients of these drugs.
    b. Contraindications to platinum-containing drugs (i.e., cisplatin, carboplatin) or pemetrexed according to the respective local labels.
11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.