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 forresection or curative radiation) or metastatic non-squamous NSCLC with specificmutations.

• Documentation of locally assessed radiological disease progression while on or afterlast 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 ofepidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), including athird generation TKI for participants with a T790M mutation; and 1 platinum-basedtherapy 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 excisionalbiopsy of a tumor lesion not previously irradiated has been provided

• Participants who have AEs due to previous anticancer therapies must have recoveredto Grade ≤1 or baseline.

• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible ifthey have received HBV antiviral therapy for at least 4 weeks, and have undetectableHBV viral load prior to randomization.

• Human immunodeficiency virus (HIV)-infected participants must have well controlledHIV 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 orprevious history of inflammatory bowel disease.

• Has Grade ≥2 peripheral neuropathy.

• Has history of documented severe dry eye syndrome, severe Meibomian gland diseaseand/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 4weeks or 5 half-lives (whichever is shorter) before randomization.

• Received a live or live-attenuated vaccine within 30 days before the first dose ofstudy intervention.

• Completed palliative radiotherapy within 7 days of the first dose. Participants musthave recovered from all radiation-related toxicities and not requirecorticosteroids.

• Received radiation therapy to the lung that is >30 Gy within 6 months of the firstdose of study intervention.

• Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targetedantibody-drug conjugate (ADC).

• Received prior treatment with a topoisomerase I-containing ADC.

• Has received an investigational agent or has used an investigational device within 4weeks prior to study intervention administration.

• Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years.

• Active infection requiring systemic therapy.

• History of noninfectious pneumonitis/ILD that required steroids or has currentpneumonitis/ILD.

• Has known active central nervous system metastases and/or carcinomatous meningitis.Participants with previously treated brain metastases may participate provided theyare clinically stable, radiologically stable for at least 4 weeks and do not requireglucocorticoids for at least 14 days prior to randomization.

• HIV-infected participants with a history of Kaposi's sarcoma and/or MulticentricCastleman'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.