A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma

Br J Cancer. 2021 Feb;124(4):744-753. doi: 10.1038/s41416-020-01180-1. Epub 2020 Dec 14.


Background: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that can drive carcinogenesis and therapy resistance. RO6870810 is a novel, small-molecule BET inhibitor.

Methods: We conducted a Phase 1 study of RO6870810 administered subcutaneously for 21 or 14 days of 28- or 21-day cycles, respectively, in patients with the nuclear protein of the testis carcinoma (NC), other solid tumours, or diffuse large B-cell lymphoma (DLBCL) with MYC deregulation.

Results: Fatigue (42%), decreased appetite (35%) and injection-site erythema (35%) were the most common treatment-related adverse events. Pharmacokinetic parameters demonstrated linearity over the dose range tested and support once-daily dosing. Pharmacodynamic assessments demonstrated sustained decreases in CD11b levels in peripheral blood mononuclear cells. Objective response rates were 25% (2/8), 2% (1/47) and 11% (2/19) for patients with NC, other solid tumours and DLBCL, respectively. Responding tumours had evidence of deregulated MYC expression.

Conclusions: This trial establishes the safety, favourable pharmacokinetics, evidence of target engagement and preliminary single-agent activity of RO6870810. Responses in patients with NC, other solid tumours and DLBCL provide proof-of-principle for BET inhibition in MYC-driven cancers. The results support further exploration of RO6870810 as monotherapy and in combinations.

Clinical trials registration: NCT01987362.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Azepines / administration & dosage*
  • Azepines / adverse effects*
  • Azepines / blood
  • Azepines / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Nuclear Proteins / metabolism*
  • Proteins / antagonists & inhibitors*
  • Small Molecule Libraries / administration & dosage
  • Small Molecule Libraries / adverse effects
  • Small Molecule Libraries / pharmacokinetics


  • Azepines
  • NUTM1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proteins
  • Small Molecule Libraries
  • bromodomain and extra-terminal domain protein, human

Associated data

  • ClinicalTrials.gov/NCT01987362