Sacituzumab Govitecan in Patients With Relapsed/Refractory Advanced Head and Neck Squamous Cell Carcinoma: Results From the Phase 2 TROPiCS-03 Basket Study

Abstract Purpose: Treatment options for advanced head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and a programmed death-1 (PD-1) inhibitor are limited. Trophoblast cell-surface antigen 2 (Trop-2) is highly expressed in HNSCC. Sacituzumab govitecan (SG) is a Trop-2–directed antibody–drug conjugate approved for patients with certain previously treated solid tumors. Methods: TROPiCS-03 (NCT03964727) is an open-label, multicohort, phase 2 study evaluating SG in advanced solid tumors, including HNSCC. Adults with locally advanced or metastatic HNSCC that progressed following platinum-based chemotherapy and anti–PD-(ligand)1 therapy (given sequentially [either order] or in combination) were administered SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results: Patients (N=43) received a median of 3 (range, 2–9) prior anticancer regimens. ORR was 16% (95% confidence interval [CI], 7–31%), with 7 confirmed partial responses. CBR was 28% (95% CI, 15–44%). Median (95% CI) DoR, PFS, and OS were 4.2 (2.6–not reached), 4.1 (2.6–5.8), and 9.0 (7.1–10.5) months, respectively. The most common treatment-emergent adverse events (TEAEs) were diarrhea (47%), nausea (47%), and neutropenia (47%). Grade ≥3 TEAEs occurred in 58% of patients. Three patients died owing to TEAEs, with one event (septic shock) considered related to SG. Conclusions: These data demonstrate the clinical potential of Trop-2–directed therapy in managing heavily pretreated patients with advanced HNSCC.