Non-Small Cell Lung Cancer (NSCLC) Clinical Trials

• Sign and date the Tissue Screening ICF, prior to any Tissue Screening procedure. Sign and date the Main ICF, prior to the start of any trial-specific qualification procedures.

• Sign and date the Optional PGx ICF (included in the Main ICF) prior to any PGx procedure, and the Pregnant Partner ICF, if applicable.

• Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old.

• Histologically documented non-squamous locally advanced unresectable or metastatic

• NSCLC and meets all of the following criteria:

• Has Stage IV NSCLC disease or Stage IIIB or IIIC disease but is not a candidate for surgical resection or definitive chemoradiation at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition). Has no known AGAs (based on the local test results obtained using validated or approved tests as required per local regulation) that have locally available therapies targeting their AGAs in the first-line advanced/metastatic setting.

• Has no known HER2 mutation based on existing test results (if approved or validated local test is available). Note: Participants with mixed histology are eligible if non-squamous NSCLC is the predominant histology. Mixed tumors will be classified based on the predominant cell type.

• Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Participants who received adjuvant or neoadjuvant therapy other than those listed below, including ICI (ie, anti-PD-1/PD-L1) or a platinum-based regimen, are eligible if the last dose of adjuvant/neoadjuvant therapy was given at least 6 months before the date of the first trial dose if their disease has progressed at least 6 months after the last dose date of adjuvant/neoadjuvant therapy.

‣ Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.

⁃ HER2-targeted antibody-based anticancer therapy.

• Has adequate tumor tissue sample (not previously irradiated) available for assessment of HER2 and PD-L1 expression by central or Sponsor-specified laboratory. A new biopsy is required if the participant's most recent archival tumor tissue sample cannot be supplied.

∙ Details pertaining to tumor tissue submission can be found in the Trial Laboratory Manual.