Actuate Therapeutics Announces Publication of Positive Phase II Clinical Data for Elraglusib Combined with Platinum Chemotherapy and Sequential Immunotherapy in Recurrent, Metastatic Salivary Gland Carcinoma

Promising data show a median overall survival of 18.6 months, with 40% of patients alive at 2 years.

Results suggest that nuclear GSK-3β expression may help identify patients

most likely to respond to treatment of a historically difficult-to-treat refractory disease

CHICAGO and FORT WORTH, Texas, Dec. 15, 2025 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ:ACTU) ("Actuate" or the "Company"), a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), today 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 3β Inhibitor, plus Chemotherapy with or without Immunotherapy in Patients with Recurrent, Metastatic Salivary Gland Carcinoma," is available here.

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-3β 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-3β (glycogen synthase kinase 3β) 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.

"This study represents an important step in evaluating elraglusib as a treatment and GSK-3β as a therapeutic target for metastatic salivary gland cancer," said Glenn Hanna, M.D., Director, Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, and Principal Investigator of the study. "Among non-ACC patients who received immune priming followed by cisplatin plus elraglusib, the response rate was 18%. Notably, all three responders had elevated nuclear GSK-3β expression. These novel and promising observations warrant follow-up in future trials."

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-3β expression was 50% in responders vs. 2% in non-responders. Patients with above-median nGSK-3β 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%).
  
  

"These results mark an important milestone for patients with metastatic salivary gland cancer," said Dan Schmitt, Chief Executive Officer of Actuate Therapeutics. "This is one of the first trials in this disease to explore sequential therapy combining varied treatment mechanisms (chemotherapy, targeted therapy, and immunotherapy), where single-agent approaches have historically shown limited activity. These findings are promising and provide a foundation for future clinical studies, suggesting that nuclear GSK-3β expression may help identify patients most likely to benefit. We are grateful to the investigators, patients, families, and the Actuate team who made this progress possible, and we remain committed to advancing innovative therapies for those facing this devastating disease."

About the Phase II Trial

The Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK-3β) Inhibitor, Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma (ClinicalTrials.gov ID NCT05010629) was a single-institution, open-label, non-randomized, parallel cohort Phase II study of elraglusib (9-ING-41) in combination with platinum chemotherapy (carboplatin or cisplatin) for the treatment of adult patients with incurable, recurrent, or metastatic salivary gland carcinoma (SGC). A second cohort received sequential pembrolizumab priming prior to elraglusib plus platinum therapy. The study was conducted at the Center for Head and Neck Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts. Actuate Therapeutics supported this research by providing the study drug elraglusib (9-ING-41) and funding. The study has completed enrollment with 32 patients and the results are now published in Clinical Cancer Research.

About Actuate Therapeutics, Inc.

Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers. Actuate's lead investigational drug, elraglusib (a novel GSK-3β inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy through the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and DNA Damage Response (DDR). Elraglusib may also mediate anti-tumor immunity through the regulation of multiple immune checkpoints and immune cell function.

For additional information, please visit the Company's website at www.actuatetherapeutics.com or follow us on LinkedIn, X, and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements about us, including our and other parties' clinical trials and development plans, and our industry. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "ongoing," "plan," "potential," "predict," "project," "should," "target," "will," "would," or the negative of these terms or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements related to present facts or current conditions or of historical facts, contained in this press release are forward-looking statements. Accordingly, these statements involve estimates, assumptions, substantial risks and uncertainties which could cause actual results to differ materially from those expressed in them, including but not limited to that preliminary and unpublished data may be subject to change and further interpretation following the availability of more data or following a more comprehensive review of the data and should not be relied upon as a final analysis; clinical and preclinical drug development involves a lengthy and expensive process with uncertain timelines and outcomes, results of prior preclinical studies, early clinical trials and sub-group studies are not necessarily predictive of future results and may not correlate with improved responses, and elraglusib may not achieve positive clinical results or favorable preclinical results or receive regulatory approval on a timely basis, if at all; that we may not successfully enroll additional patients or establish or advance plans for further development, including through conversations with the FDA or EMA and the standards such bodies may impose for such development; that elraglusib could be associated with side effects, adverse events or other properties or safety risks, which could delay or preclude regulatory approval, cause us to suspend or discontinue clinical trials or result in other negative consequences; our reliance on third parties to conduct our non-clinical studies and our clinical trials; our reliance on third-party licensors and ability to preserve and protect our intellectual property rights; that we face significant competition from other biotechnology and pharmaceutical companies; our ability to fund development activities, including because our financial condition raises substantial doubt as to our ability to continue as a going concern and we require additional capital to finance our operations beyond the second quarter of fiscal year 2026, and a failure to obtain this necessary capital in the near term on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our development programs, commercialization efforts or other operations. In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading "Item 1A. Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 13, 2025, and our Quarterly Reports on Form 10-Q, and other filings with the SEC. Because the risk factors referred to above could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements made by us or on our behalf, you should not place undue reliance on any forward-looking statements. Further, any forward-looking statement speaks only as of the date on which it is made. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Unless legally required, we do not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events.

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