Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004)

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

Histologically- or cytologically-documented advanced (Stage III not eligible for resection or curative radiation) or metastatic non-squamous NSCLC with specific mutations.
Documentation of locally assessed radiological disease progression while on or after last treatment based on Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1.
Participants with genome mutations must have received 1 or 2 prior lines of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), including a third generation TKI for participants with a T790M mutation; and 1 platinum-based therapy after progression on or after EGFR TKI.
Measurable disease per RECIST 1.1 as assessed by the local site investigator.
Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline.
Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
Have an ECOG performance status of 0 or 1 within 3 days before randomization.

Exclusion Criteria:

Has predominantly squamous cell histology NSCLC.
Has mixed tumor(s) with small cell elements.
Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
Has Grade ≥2 peripheral neuropathy.
Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
Has an EGFR T790M mutation and has not received a third generation EGFR TKI (eg, osimertinib).
Received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before randomization.
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
Completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
Received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention.
Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC).
Received prior treatment with a topoisomerase I-containing ADC.
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
Known additional malignancy that is progressing or has required active treatment within the past 3 years.
Active infection requiring systemic therapy.
History of noninfectious pneumonitis/ILD that required steroids or has current pneumonitis/ILD.
Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks, and are off steroids 3 days prior to dosing with study medication.
HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.