CTNI-26. A PHASE II STUDY OF SACITUZUMAB GOVITECAN IN RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is the most aggressive and common form of primary brain cancer. GBM expresses trophoblast cell-surface antigen 2 (Trop2) which correlates with proliferation rate, microvessel density, histological grade and clinical survival. Sacituzumab Govitecan (SG) is an antibody-drug conjugate targeting Trop2 with a chemotherapy payload, SN-38. This drug has been approved for triple-negative and hormone-receptor positive metastatic breast cancer. METHODS We conducted multi-center (UT Health San Antonio, Cleveland Clinic, Texas Oncology in Austin), open-label, single-arm phase 2 study using a 2-stage adaptive Bayesian design. Patients with recurrent GBM (rGBM), IDH wild-type, following standard-of-care chemoradiation, received SG (10mg/kg IV, days 1 and 8 every 21 days). Patients were assessed by RANO and CTCAE v5. The primary endpoint was PFS of patients on SG as compared to a historical control of lomustine. RESULTS As of interim analysis cutoff, 24 patients have been screened with 20 patients enrolled. The average age was 58.8 years. 65% of patients identified as male. 95% were Caucasian with 20% identifying as Spanish, Hispanic or Latino. Adverse events (AE) include lymphopenia (40%), neutropenia (40%), hypokalemia (35%), elevated alkaline phosphatase (30%), anemia (30%) with most AE being grade ≤ and no grade 5 observed. 4 patients had grade ≥3 neutropenia attributable to SG. 20% had stable disease as best response with the rest being progressive disease. The mean PFS and OS were 7.0 and 2.0 months, respectively. Of 19 evaluable samples, 63% had positive Trop2 expression (H-Score ≥100, mean 123.6±74 [0.6, 269.2]). A post-hoc analysis of OS log survival time vs H-Score (n=19) using an accelerated failure time model showed that survival correlated with H-Score (p=0.0361). CONCLUSIONS In the interim analysis of this study of patients with rGBM, Sacituzumab was found to be well-tolerated. Further study of those patients bearing tumors with elevated H-scores may be warranted.