Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

Inclusion Criteria: Participants eligible for inclusion in the study must meet all inclusion criteria for this study. * Sign and date the inform consent form (ICF) prior to the start of any study- specific qualification procedures. * Adults ≥18 years (if the legal age of consent is \>18 years old, then follow local regulatory requirements) * Has pathologically documented NSCLC that: 1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition). 2. Has one or more of the following documented activating genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET. KRAS mutations in the absence of any of the genomic alterations specified above will be excluded. Overexpression of EGFR, in the absence of activating mutations, is NOT sufficient for enrollment. Participants who have not received osimertinib should be evaluated for the presence of EGFR T790M mutation after relapse/progression on/after the most recent EGFR tyrosine kinase inhibitor (TKI), unless the participant is already known to be positive with document results for this mutation or unless osimertinib is not locally approved. * Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC. * Participant must meet the following for advanced or metastatic NSCLC: 1. Has been treated with at least one but no more than two cytotoxic agent-containing therapy in the metastatic setting: * One platinum-containing regimen (either as monotherapy or combination therapy). * May have received up to one additional line of cytotoxic agent-containing therapy. * Those who received a platinum-containing regimen as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease. 2. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be in combination with a cytotoxic agent as part of a regimen described above or as an additional CPI regimen without a cytotoxic agent). 3. Has been treated with 1 or more lines of non-CPI targeted therapy that is locally approved for the participant's applicable genomic alteration at the time of screening: * Those who received a targeted agent for the applicable genomic alterations in the study as adjuvant therapy for early stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alterations (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease. * Participants who have been treated with a prior TKI must receive additional targeted therapy, if clinically appropriate, for the genomic alterations that are considered amenable or the participant will not be allowed in the study. * Must undergo a mandatory pre-treatment tumor biopsy procedure or if available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the mandatory biopsy collected during screening. * Measurable disease based on local imaging assessment using RECIST v1.1. * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening. Exclusion Criteria: Participants meeting any exclusion criteria for this study will be excluded from this study. * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. * Has leptomeningeal carcinomatosis. * Has prior treatment with: 1. Any chemotherapeutic agent targeting topoisomerase I, including antibody drug conjugate (ADC) containing such agent. 2. TROP2-targeted therapy. * Uncontrolled or significant cardiovascular disease: 1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1. 2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1. 3. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) at screening. Participants with a history of Class II to IV CHF prior to screening must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible. 4. History of serious cardiac arrhythmia requiring treatment. 5. LVEF \<50% or institutional lower limit of normal by ECHO or MUGA scan. 6. Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg). * Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses * Clinically significant corneal disease. * Has other primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.