Key Inclusion Criteria:  Pathologically documented non-small cell lung cancer (NSCLC) with documented evidence of Stage 4 NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition). Testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and programmed death ligand 1 (PD-L1) is required. Testing for other actionable genomic alterations is recommended and to be performed as per local standard of care and availability of targeted treatment.  Must have progressed after platinum-based chemotherapy in combination with anti-PD-L1 antibody OR platinum-based chemotherapy and anti-PD-L1 antibody (in either order) sequentially.  No additional treatments are allowed in the recurrent/metastatic setting for individuals with no actionable genomic alterations. Individuals with EGFR, ALK, or any other known actionable genomic alterations must have also received treatment with at least 1 approved tyrosine kinase inhibitor 1(TKI) appropriate to the genomic alteration. Documented radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC. Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator in accordance with per RECIST Version 1.1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count ≥ 1500/mm^3, and platelets ≥ 100,000/μL). Adequate hepatic function (bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase ≤ 2.5 ULN or ≤ 5 x ULN if known liver metastases, and serum albumin > 3 g/dL). Creatinine clearance of at least 30 mL/min as assessed by the Cockcroft-Gault equation. Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.  Key Exclusion Criteria:  Mixed small-cell lung cancer and NSCLC histology. Positive serum pregnancy test or women who are lactating. Received a prior anticancer biologic agent within 4 weeks prior to enrollment or have received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (ie, > Grade 2 is considered not recovered) from adverse events (AEs) at the time of study entry. Individuals participating in observational studies are eligible. Have not recovered (ie, > Grade 2 is considered not recovered) from AEs due to a previously administered agent.  Previously received treatment with any of the following:  Topoisomerase 1 inhibitors. Any agent including an antibody-drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase 1 Trop-2-targeted therapy Docetaxel as monotherapy or in combination with other agents Active second malignancy NSCLC that is eligible for definitive local therapy alone. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc); or prior pneumonectomy. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Active cardiac disease Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment. Active serious infection requiring antibiotics. Positive HIV-1 or HIV-2 antibody with detectable viral load OR taking medications that may interfere with SN-38 metabolism. Positive for hepatitis B surface antigen. Individuals who test positive for hepatitis B core antibody will require hepatitis B virus DNA by quantitative polymerase chain reaction for confirmation of active disease. Positive hepatitis C antibody and detectable hepatitis C viral load.  Note: Other protocol defined Inclusion/Exclusion criteria may apply.