Table 3

Inhibitors of epigenetic regulators validated in clinical trials in pancreatic cancer (recruiting trials)

CompoundEpigenetic targetCombinationTreatmentNCT numberOutcome measuresEnrolled tumour entitiesNo. of enrolled patients
Phase I and combined phase I/II
 VorinostatHDAC I/IISorafenib
Gemcitabine
n-Paclitaxel
Radiation		Neoadjuvant02349867Recommended phase II doses and schedulePDAC35*
 OBP-801HDAC (pan)Palliative02414516MTD, pharmacokinetics, objective response, durability of objective responseAdvanced solid tumours36*
 RomidepsinHDAC class IPalliative01638533MTD; dose-limiting toxicity, pharmacokinetics, antitumour activity, Child-Pugh classificationLymphoma, CLL, solid tumours132*
 TEN-010Pan-BETPalliative01987362MTD, toxicity, pharmacokinetics, efficiencySolid tumours66*
 TazemetostatEZH2Palliative01897571MTD, objective response rate, effect of high-fat-meal on EPZ6438 bioavailability, OS, PFS, duration to response, effect of exposure to midazolamPhase I: B-cell lymphoma, advanced solid tumours;
phase II: diffuse large B-cell lymphoma, follicular lymphoma		225*
 GSK2816126EZH2Palliative02082977Number of subjects with adverse events, withdrawal caused by adverse events, dose-limiting toxicity, change of clinical, cardiac and laboratory parameters, objective response rate, pharmacokinetics, compared with baselineNot specified cancer169*
Phase II non-radomised
 TazemetostatEZH2Palliative02601950Objective response, PFS, pharmacokinetics, response duration, pharmacodynamics†Malignant rhabdoid tumours, rhabdoid tumours of the kidney, atypical teratoid rhabdoid tumours, selected tumours with rhabdoid features, synovial sarcoma, INI1-negative tumours malignant rhabdoid tumour of ovary, renal medullary carcinoma, epithelioid sarcoma150*

  • *Estimated enrolment.

  • †Fifty-five per cent disease control rate in solid tumours, responses have been restricted to SMARCB1-mutated and SMARCA4-mutated tumours. No data reported for PDAC so far.

  • BET, bromodomain and extraterminal; CLL, chronic lymphocytic leukemia; MTD, maximum tolerated dose; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival.