お知らせ • Dec 16
Actuate Therapeutics, Inc. Announces Publication of Positive Phase II Clinical Data for Elraglusib Combined with Platinum Chemotherapy and Sequential Immunotherapy in Recurrent, Metastatic Salivary Gland Carcinoma
Actuate Therapeutics, Inc. announced the publication of new data in Clinical Cancer Research from a Phase II study (NCT05010629) evaluating elraglusib in combination with carboplatin or cisplatin (with or without sequential pembrolizumab priming) in patients with advanced, metastatic salivary gland cancers, including adenoid cystic carcinoma and other subtypes. The peer-reviewed paper (PMID: 41065505), entitled ‘Elraglusib, a Glycogen Synthase Kinase 3ß Inhibitor, plus Chemotherapy with or without Immunotherapy in Patients with Recurrent, Metastatic Salivary Gland Carcinoma. Despite decades of research, there are no approved systemic cytotoxic or targeted therapies available for the treatment of recurrent and metastatic salivary gland cancer. While some treatments have shown modest activity in certain molecular subgroups, such as HER2 (Human Epidermal Growth Factor Receptor 2)-overexpressing, androgen receptor-overexpressing, or NTRK (Neurotrophic Tyrosine Receptor Kinase)-fused tumors, most patients lack actionable therapeutic targets. Exploring new treatment options and novel therapeutic combinations represents a significant priority in salivary gland cancer. This study represents one of the first clinical trials in advanced salivary gland cancer to explore sequential therapy and systemic treatments with varied therapeutic mechanisms in which single-agent approaches have so often yielded limited antitumor activity. Elraglusib (9-ING-41) is a small-molecule inhibitor of GSK-3ß with immune-modifying properties that disrupts multiple cellular signaling pathways, inhibits tumor growth, and increases sensitivity to chemotherapy. This phase II clinical trial evaluated elraglusib combined with platinum chemotherapy in patients with advanced, metastatic salivary gland cancer, including both adenoid cystic carcinoma (ACC) and non-ACC subtypes, with one cohort receiving sequential immune checkpoint inhibitor priming. A key finding in this study was that nuclear GSK-3ß (glycogen synthase kinase 3ß) expression was significantly higher in responders than non-responders (50% vs. 2%). Across the 32-patient study population, median progression-free survival was 6.4 months, with 27% of patients progression-free at 1 year. Additionally, median overall survival reached 18.6 months for the entire cohort and 27.8 months among non-ACC patients, with 40% of all patients alive at 2 years. Key Highlights and Readouts: Both adenoid cystic carcinoma (ACC, 47%) and non-ACC (53%) patients were enrolled, with a total enrollment of 32 patients, in partnership with the Center for Head and Neck Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts. Median OS was 18.6 months (95% CI, 9.7–29.4). At 1 year, 58% of patients were alive; at 2 years, 40% remained alive. Non-ACC patients had a median OS of 27.8 months. Median PFS was 6.4 months (95% CI, 2.3–8.8); 27% of patients remained progression-free at 1 year. Historical PFS for this population is estimated at 4–9 months for ACC and <6 months for non-ACC. Three patients, all of whom were non-ACC and had PD-L1 scores <1%, had Partial Responses, indicating responses occurred despite low tumor immunogenicity. The median duration of response was 6.9 months. Two of three responders had CDKN2A/B and MTAP co-deletion, a molecular profile that typically predicts poor response to chemotherapy and immunotherapy—suggesting elraglusib may provide added benefit in this subgroup. Median nuclear GSK-3ß expression was 50% in responders vs. 2% in non-responders. Patients with above-median nGSK-3ß expression had longer median PFS (8.5 vs. 4.2 months) and numerically longer OS (not reached vs. 18.6 months). The combination was well tolerated: no treatment-related deaths occurred, and only 6% (2 patients) were discontinued due to toxicity. The most common treatment-related adverse events were anemia (69%), nausea (50%), and neutropenia (44%).