citarinostat (ACY-241)

P1, N=19, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

P1, N=85, Terminated, Celgene | Phase classification: P1a/1b --> P1 | Trial completion date: Jan 2024 --> Jun 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2024 --> Jun 2024; Lack of efficacy

P1, N=17, Terminated, Celgene | Active, not recruiting --> Terminated; Lack of efficacy

P1, N=19, Active, not recruiting, Massachusetts General Hospital | Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Sep 2024 | Trial primary completion date: Jun 2023 --> Sep 2024

P1, N=16, Active, not recruiting, Celgene | Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Jan 2024 | Trial primary completion date: Jun 2023 --> Jan 2024

This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

There was one grade 3 trAE: specifically, a thromboembolic event in one patient who was receiving lenalidomide and despite aspirin prophylaxis, but who fully recovered. PB and marrow transcriptome profiling along with the immunogenicity studies are in progress and will be presented. We will evaluate whether PB mononuclear cells have the potential to replace BM as a surrogate for genetic and immunological surveillance in SMM, as we anticipate that further understanding of the immune alterations among patients with SMM and the response to immunomodulatory therapy may provide insight on early intervention and prevention of progression to symptomatic disease.

P1a/1b, N=85, Active, not recruiting, Celgene | Trial completion date: Jul 2023 --> Jan 2024 | Trial primary completion date: Jun 2023 --> Jan 2024

To the best of our knowledge, this is the first research reporting the irreversible inhibition of HDAC6. It was also demonstrated that compared with ACY-241 (a reversible HDAC6 inhibitor in clinical trials), the irreversible HDAC6 selective inhibitor 4 exhibited not only superior anti-multiple myeloma activity but also improved therapeutic index.

Overall, co-inhibition of HDAC6 and HDAC8 through selective inhibitors synergistically suppresses cancer cell proliferation and metastasis in p53 wild-type ovarian cancer cells. These results suggest a novel approach to treating ovarian cancer patients and the therapeutic potential in developing HDAC6/8 dual inhibitors.

Finally, coupling these ACY241-mediated effects with the chemotherapy drug Oxaliplatin led to significantly enhanced tumor-associated T cell effector functionality in lung cancer-bearing mice and in patient-derived tumors. Collectively, our studies highlight the molecular underpinnings of the expansive immunomodulatory activity of ACY241 and supports its suitability as a partner agent in combination with rationally selected chemotherapy agents for therapeutic intervention in NSCLC.