This study will assess if adding sacituzumab tirumotecan with pembrolizumab after surgery is effective in treating NSCLC for participants not achieving pathological complete response. The primary hypothesis of this study is sacituzumab tirumotecan plus pembrolizumab is superior to pembrolizumab monotherapy with respect to disease free survival (DFS) as assessed by blinded independent central review (BICR).
None
Has histological or cytological confirmation of squamous or nonsquamous non-small cell lung cancer (NSCLC), resectable clinical Stage II, IIIA or IIIB (with nodal involvement [N2]) per AJCC eighth edition guidelines
Has confirmation that either epidermal growth factor receptor (EGFR)-directed or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated as primary therapy
Is able to undergo surgery based on opinion of investigator after consultation with surgeon
Is able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy
Parallel
Sacituzumab tirumotecan
Biological/VaccineSacituzumab tirumotecan to be administered as 4mg/kg IV infusion q2w for up to 24 weeks
Pembrolizumab
Biological/VaccinePembrolizumab to be administered 400mg by IV infusion q6w for up to 42 weeks
Cisplatin
DrugCisplatin is administered as 75 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment in neoadjuvant phase
Pemetrexed
DrugPemetrexed will be administered in the neoadjuvant phase as 500 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment in participants with nonsquamous NSCLC.
Gemcitabine
DrugGemcitabine will be administered in the neoadjuvant phase as 1000 mg/m\^2 or 1250 mg/m\^2 IV infusion on day 1 and day 8 q3w for up to 24 weeks as background treatment in participants with squamous NSCLC.
Carboplatin
DrugCarboplatin will be administered in the neoadjuvant phase as AUC 5 mg/mL/min or AUC 6 mg/mL/min IV infusion q3w for up to 12 weeks as background treatment.
Paclitaxel
DrugPaclitaxel will be administered in the neoadjuvant phase as 175 mg/m\^2 or 200 mg/m\^2 IV infusion q3w for up to 12 weeks as background treatment.
Rescue medication
DrugParticipants are permitted to take rescue medications to prevent hypersensitivity and/or infusion reactions as a premedication to study treatment. Rescue medications include antihistamine, H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent, and granulocyte colony-stimulating factor. A steroid mouthwash (dexamethasone or equivalent) may be given as prophylaxis for stomatitis/oral mucositis.
Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR)
DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Distant metastasis-free survival (DMFS) as assessed by investigator
DMFS is defined as the time from randomization to the first documented distant metastasis or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.
Disease-Free Survival (DFS) as assessed by investigator
DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.
Lung Cancer Specific Survival (LCSS)
LCSS is defined as the time from randomization to the date of death due to lung cancer.
Click on the lead sponsor to view all of their trials.