A Study of Sigvotatug Vedotin Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of locally advanced,unresectable (Stage IIIB, IIIC), or metastatic Stage IV (M1a, M1b, or M1c) NSCLCAmerican Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Unionfor International Cancer Control (UICC) Staging System (Eighth edition).

• Participants must have NSCLC with nonsquamous histology

• Tumors with squamous, or predominantly squamous histology are excluded.

• Tumors with small cell elements are excluded.

• Participants who have NSCLC with known actionable genomic alteration (AGAs) arepermitted

• Participants must have received the following prior therapies and progressed duringor relapsed after receiving their most recent prior therapy:

• Participants with no known AGAs must fulfill 1 of the following conditions:

• Received a platinum-based combination therapy for the treatment ofmetastatic or recurrent disease and a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy), unlesscontraindicated.

• Experienced disease progression within 6 months of the last dose ofplatinum-based chemotherapy in the adjuvant or neoadjuvant setting andreceived a PD-(L)1 monoclonal antibody at any time during the course oftreatment.

• Participants with known AGAs must fulfill the following conditions:

• Must have received at least 1 relevant AGA targeted therapy and in theopinion of the investigator, additional AGA targeted therapy is not in thebest interest of the participant.

• Received a platinum-based combination therapy for the treatment ofmetastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvantor neoadjuvant setting

• May have received up to 1 PD-(L)1 monoclonal antibody (concurrently orsequentially with platinum-based chemotherapy).

• Measurable disease based on RECIST v1.1

• Participants must have an Eastern Cooperative Oncology Group (ECOG) performancestatus of 0 or 1, with adequate baseline hematologic, hepatic, and renal functionand measurable disease according to RECIST v1.1

Exclusion Criteria:

• Life expectancy of less than (<) 3 months

• Known allergies/hypersensitivity/intolerance to or contraindication of taxanes,docetaxel, or any excipient contained in the drug formulation of sigvotatug vedotin

• History of another malignancy within 3 years before Cycle 1 Day 1, or any evidenceof residual disease from a previously diagnosed malignancy. Exceptions aremalignancies with a negligible risk of metastasis or death

• Participants with any of the following respiratory conditions:

• Evidence of noninfectious interstitial lung disease (ILD) or pneumonitis that:

• Was previous diagnosed and required systemic steroids, or

• Is currently diagnosed and managed, or

• Is suspected on radiologic imaging at screening

• Known diffusing capacity of the lung for carbon monoxide (DLCO) < 50%

• Any Grade greater than or equal to (≥) 3 pulmonary disease unrelated tounderlying malignancy

• Pre-existing peripheral neuropathy Grade greater than or equal to (≥) 2

• Uncontrolled diabetes mellitus

• Prior therapy:

• Prior treatment with antimicrotubule agents (taxanes, vinca alkaloids, orMMAEs) in the locally advanced, unresectable/refractory, or metastatic setting

• Prior antimicrotubule agent exposure in curative settings (including adjuvant,neoadjuvant, or chemoradiotherapy) is permissible.

• Received more than 1 prior line of cytotoxic chemotherapy in the locallyadvanced, unresectable/refractory, or metastatic setting

• Prior cytotoxic chemotherapy in curative settings is permissible

• At least 14 days must have elapsed from the last dose of radiotherapy untilCycle 1 Day 1.

• Prior radiation therapy to the lung parenchyma that is >30 Gray (Gy) within 6months of Cycle 1 Day 1.

• Any systemic anticancer therapy (standard or experimental) within 21 days priorto Cycle 1 Day 1.

• Active central nervous system (CNS) lesions, including leptomeningeal metastasis,are excluded. Participants with definitively treated brain metastases are eligiblein they meet the following criteria:

• Have been clinically stable for at least 4 weeks prior to treatment initiationand baseline scans show no evidence of new or enlarged metastasis

• On a stable dose of less than or equal to (≤) 10mg/day of prednisone orequivalent for a least 2 weeks (if requiring steroid treatment)

• Treatment with corticosteroids greater than (>) 1 month prior to Screeningvisit

• No evidence of clinical and radiographic disease progression in the CNS for ≥ 21 days after definitive radiotherapy and/or surgery