| Abstract: |
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. ©2024 American Association for Cancer Research. |
| Keywords: |
adult; aged; aged, 80 and over; middle aged; clinical trial; mortality; phase 2 clinical trial; neoplasm recurrence, local; camptothecin; pathology; tumor antigen; monoclonal antibody; immunology; antigens, neoplasm; head and neck neoplasms; multicenter study; tumor recurrence; cell adhesion molecules; drug therapy; head and neck tumor; cell adhesion molecule; head and neck squamous cell carcinoma; antibody conjugate; immunoconjugates; antibodies, monoclonal, humanized; very elderly; humans; human; male; female; squamous cell carcinoma of head and neck; sacituzumab govitecan; tacstd2 protein, human
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