Abstract CT283: Phase 3 MK-2870-007 study: MK-2870 (SKB264) plus pembrolizumab vs pembrolizumab alone as first-line treatment for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score (TPS) ≥50%

Abstract Background: Pembrolizumab (anti-PD-1) monotherapy is a standard of care first-line treatment for advanced or metastatic non-small-cell lung cancer (NSCLC) with PD-L1 TPS ≥50% without actionable genetic alterations; however, some patients do not respond to therapy or experience disease progression. Trophoblast cell-surface antigen 2 (TROP2) is another candidate for anticancer treatment and overexpression of TROP2 is associated with poor prognosis in patients with NSCLC. MK-2870 (SKB264) is an antibody-drug conjugate (ADC) composed of the humanized TROP2 monoclonal antibody, a hydrolytically cleavable linker, and the cytotoxic drug KL610023. In patients with relapsed or refractory locally advanced or metastatic NSCLC, MK-2870 monotherapy showed encouraging antitumor activity with a manageable safety profile. The complementary mechanisms of action of MK-2870 and pembrolizumab may provide more potent antitumor activity when given in combination compared with each therapy alone. To investigate this further, the MK-2870-007 study will evaluate the efficacy and safety of the addition of MK-2870 to pembrolizumab vs pembrolizumab alone in patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥50%. Trial Design: Approximately 614 eligible patients aged ≥18 y with previously untreated histologically or cytologically confirmed stage IV (per American Joint Committee on Cancer v8. 0) NSCLC, PD-L1 TPS ≥50% and no EGFR, ALK, or ROS1 alterations (nonsquamous only) ; ECOG PS 0 or 1; and measurable disease per RECIST v1. 1 will be enrolled. Patients with well-controlled HIV are permitted. Patients will be randomized 1: 1 to receive either pembrolizumab 400 mg Q6W for up to 18 cycles plus MK-2870 4 mg/kg Q2W or pembrolizumab 400 mg IV Q6W alone until progressive disease, intercurrent illness, patient withdrawal, unacceptable toxicity, prolonged interruption of study drug, or until maximum number of cycles (18 cycles for pembrolizumab). Randomization stratification factors include ECOG PS (0 vs 1), histology (squamous vs nonsquamous), TROP2 expression (low vs medium vs high), and geographic region (East Asia vs North America/Western Europe/Australia vs Rest of World). The primary endpoint is OS. Secondary endpoints include PFS, ORR, and duration of response per RECIST v1. 1 by blinded independent central review, patient-reported outcomes, and safety. Tumor imaging will occur at baseline, Q6W until wk 48, and Q12W thereafter until PD, start of new anticancer treatment, or withdrawal of consent. PD-L1 TPS will be assessed centrally using PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Carpinteria, CA). AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5. 0. Enrollment began in December 2023 and is currently ongoing. Citation Format: Nikolaj Frost, Razi Ghori, Ananya Roy, Ana Tablante Nunes, James Chih-Hsin Yang. Phase 3 MK-2870-007 study: MK-2870 (SKB264) plus pembrolizumab vs pembrolizumab alone as first-line treatment for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score (TPS) ≥50% abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT283.