Sacituzumab Govitecan in Patients with Relapsed/Refractory Advanced Head and Neck Squamous Cell Carcinoma: Results from the Phase II TROPiCS-03 Basket Study

Purpose: Treatment options for advanced head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and a 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. Patients and Methods: TROPiCS-03 (NCT03964727) is an open-label, multicohort, phase II 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-(L)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 the investigator-assessed objective response rate. Secondary endpoints included duration of response, clinical benefit rate, progression-free survival, overall survival, and safety. Results: Patients (N = 43) received a median of 3 (range, 2–9) prior anticancer regimens. The objective response rate was 16% [95% confidence interval (CI), 7%–31%], with seven confirmed partial responses. The clinical benefit rate was 28% (95% CI, 15%–44%). The median (95% CI) duration of response, progression-free survival, and overall survival 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 (TEAE) were diarrhea (47%), nausea (47%), and neutropenia (47%). Grade ≥3 TEAE occurred in 58% of patients. Three patients died from TEAE, 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.