Table 2.

Clinical trials of single agent DNMT inhibitors and HDAC inhibitors in solid tumors

Agent(s)	Cancer type(s)	Trial details	Trial identifier/status
DNMT inhibitors
CC-486 (oral form of azacitidine)	Locally advanced or metastatic NPC	Phase II trial	NCT02269943
		Enrollment: 36 patients	Completed 4/2017
		Results: ORR 12%; median PFS and OS were 4.7 and 18.0 months, respectively. CC-486 as monotherapy did not show sufficient clinical activity in this patient population. The most common grade 3/4 TEAEs were neutropenia (33%) and febrile neutropenia (11%) [182]
Guadecitabine (SGI-110)	Advanced HCC	Phase II trial	NCT01752933
		Enrollment: 52 patients	Completed 9/2015
		Results: DCR 25% and 24.4%, median duration of response 262 days and 144 days, median PFS 55 days and 82.5 days, median OS 294 days and 245 days in the 60 mg/m2 group and 45 mg/m2 group, respectively. The most common being febrile neutropenia in both groups (25% vs. 11%) [183]
ASTX727 (cedazuridine and decitabine)	Recurrent or progressive non-enhancing IDH mutant gliomas	Phase I trial	NCT03922555
		Enrollment: 18 patients	Recruiting
		Results: pending
HDAC Inhibitors
Entinostat (SNDX-275, MS-275)	Relapsed or refractory abdominal neuroendocrine tumors	Phase II trial	NCT03211988
		Planned enrollment: 40 patients	Recruiting
		Results: N/A
Mocetinostat (MGCD0103)	Locally advanced or metastatic urothelial carcinoma	Phase II trial	NCT02236195
		Enrollment: 17 patients	Completed 7/2016
		Results: Eligible patients received oral mocetinostat at a dose of 70 mg thrice weekly (TIW) escalating to 90 mg TIW in 28-day cycles in a planned 3-stage study. Single agent mocetinostat was not efficacious in this setting and significant toxicities impacted drug exposure and possibly contributed to modest clinical activity in these pretreated patients [184]
Panobinostat (LBH589)	Locally recurrent or metastatic HER2-negative breast cancer	Phase II trial	NCT00777049
		Enrollment: 54 patients	Completed 4/2015
		Results: In HR + group (n = 33) there were 1 PR, 13 SD, 14 PD and 5 missing data; most common SAE was thrombocytopenia (12.5%). In HR-group (n = 21) there was 1 CR, 4 SD, 14 PD, 2 missing data; most common SAE was constipation (10%)
	Metastatic medullary thyroid cancer and radioactive iodine resistant differentiated thyroid cancer	Phase II trial	NCT01013597
		Enrollment: 13 patients	Completed 2/2016
		Results: Patients received LBH589 20 mg by mouth three times weekly for 28-day cycles. No responses seen, median time to progression 3.6 months, median OS 18.4 months (5.8 to NA). Most common toxicities were lymphopenia, thrombocytopenia and fatigue (8 patients each). There were 3 deaths “not otherwise specified”
	Metastatic melanoma	Phase I trial	NCT01065467
		Enrollment: 16 patients	Completed 3/2017
		Results: 6 patients were treated on Arm A (oral panobinostat 30 mg daily on MWF) and 10 patients were enrolled to Arm B (oral panobinostat 30 mg three times a week every other week) with 9 patients treated. DLT in arm A included clinically significant thrombocytopenia requiring dose interruption. Among all 15 treated patients, ORR was 0% and DCR was 27%. Panobinostat monotherapy was not active in melanoma and there was a high toxicity rate [185]
Valproic acid (VPA)	Uveal melanoma	Phase II trial	NCT02068586
		Planned enrollment: 150 patients	Recruiting
		Results: N/A
	Advanced thyroid cancers of follicular origin	Phase II trial	NCT01182285
		Enrollment: 13 patients	Completed 4/2016
		Results: No responses were seen and 6 patients had PD. Zero of 10 patients had increased radioiodine uptake at their tumor sites. Valproic acid did not increase radioiodine uptake and did not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin [186]
Vorinostat (SAHA)	Locally advanced, recurrent or metastatic adenoid cystic carcinoma	Phase II trial	NCT01175980
		Enrollment: 30 patients	Completed 6/2018
		Results: Stable disease was the best response in 27 patients. Median PFS and stable disease duration were both 11.4 months and median OS has not been reached. Grade 3 AEs that occurred in more than 1 patient included lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic event (n = 2) and fatigue (n = 2). Eleven patients required dose reduction due to drug related AEs [187]

Only select studies within the past 5 years have been included due to extent of clinical trials

AE adverse events, CRC colorectal cancer, CRPC castrate-resistant prostate cancer, DCR disease control rate, DNMT DNA methyltransferase, HCC hepatocellular carcinoma, HDAC histone deacetylase, HR hormone receptor, ITT intention-to-treat, NPC nasopharyngeal carcinoma, NSCLC non-small cell lung cancer, ORR objective response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SAE serious adverse event, SCLC small cell lung cancer, SD stable disease, TEAE treatment-emergent adverse event