Elraglusib, a glycogen synthase kinase-3β (GSK-3β) inhibitor, plus chemotherapy with or without immunotherapy in patients with recurrent, metastatic salivary gland carcinoma.

Abstract

BACKGROUND GSK-3b is a known therapeutic target in cancer. Aberrant nuclear GSK-3β (nGSK-3β) expression has been shown in some salivary gland cancers (SGC). Elraglusib is a small molecule GSK-3β inhibitor with immunomodulatory potential. We hypothesized that elraglusib plus platinum-based chemotherapy and immunotherapy priming would be a novel treatment approach for SGC. DESIGN This phase 2, open-label trial enrolled patients with recurrent or metastatic SGC (adenoid cystic carcinoma [ACC] vs. other subtypes) with disease progression in the preceding year. Cohort 1 received elraglusib (15 mg/kg IV on days 1, 4) plus carboplatin (AUC 5) or cisplatin (75 mg/m2) every 21-days. Cohort 2 received 2-cycles of pembrolizumab (200 mg IV) every 21-days prior to the same regimen. PRIMARY ENDPOINT best overall response rate (ORR) by RECIST 1.1 (>5/32 in response to detect 25% ORR). RESULTS Thirty-two patients enrolled, 15 (47%) with ACC and 17 (53%) with non-ACC. Best ORR was 9.4% (3/32; 95%CI, 2-25) (3 partial responses, all non-ACC). Nineteen (59%) patients achieved stable disease. Median duration of response: 6.9 months. Common treatment-related adverse events: anemia (22, 69%), nausea (16, 50%), and neutropenia (14, 44%). At median follow-up of 18.3 months, median PFS: 6.4 months (95%CI, 2.3-8.8) and median OS: 18.6 months (95%CI, 9.7-29.4) overall. Median nGSK-3β expression was 50% vs. 2% for responders vs. non-responders. CONCLUSION(S) The trial did not meet its primary endpoint, though 18% of non-ACC patients treated with immune priming followed by cisplatin plus elraglusib achieved response. Higher nGSK-3β expression was observed in tumor samples from responders.