Citarinostat + Nivolumab

Citarinostat (ACY-241) is a selective histone deacetylase 6 (HDAC6) inhibitor that has been studied in combination with nivolumab, an immune checkpoint inhibitor. This combination has been investigated primarily for advanced non-small cell lung cancer (NSCLC) in patients who had received prior chemotherapy but had not received prior HDAC or immune checkpoint inhibitor therapy. The combination was studied in a phase Ib, multicenter, single-arm, open-label, dose-escalation study to determine the maximum tolerated dose (MTD) and evaluate safety and preliminary antitumor activity. In this study, orally administered ACY-241 was escalated at doses of 180, 360, or 480 mg once daily, while nivolumab was administered at 240 mg (starting on day 15 of cycle 1, then every 2 weeks thereafter)[1][10]. The study successfully identified an MTD for the combination and suggested that it may be feasible in patients with advanced NSCLC. Responses were observed in patients with advanced NSCLC during the trial[1][10]. Citarinostat itself is a selective HDAC6 inhibitor with potential antineoplastic activity. It works by inhibiting tumor oncogene transcription and selectively promoting the transcription of tumor suppressor genes, which inhibits tumor cell division and induces tumor cell apoptosis[4]. Nivolumab is a well-established immune checkpoint inhibitor that has received FDA approval for various cancer indications, including in combination with other agents for hepatocellular carcinoma, renal cell carcinoma, and urothelial carcinoma[3][6][7][9]. The combination of citarinostat and nivolumab represents an approach that combines epigenetic modulation through HDAC6 inhibition with immune checkpoint blockade, potentially offering synergistic antitumor effects. ### Development Status The combination has been studied in Phase 1 clinical trials for non-small cell lung cancer. According to the search results, this was a phase Ib study that determined the maximum tolerated dose and showed preliminary antitumor activity[1][10]. Citarinostat has also been studied individually or in other combinations for multiple myeloma (Phase 2), smoldering multiple myeloma (Phase 1), unresectable melanoma (Phase 1), and advanced malignant solid neoplasms (Phase 1)[2]. Nivolumab has received FDA approval for multiple indications, including in combination with other agents such as ipilimumab for hepatocellular carcinoma, renal cell carcinoma, and in combination with cisplatin and gemcitabine for urothelial carcinoma[3][6][7][9].

Brand names

Opdivo

Other names

Selective HDAC6 inhibitor ACY-241 plus nivolumab