NP39461 - RO6870810 and Venetoclax in patients with R/R DLBCL

• Research type

  Research Study

• Full title

  OPEN LABEL, DOSE ESCALATION/EXPANSION PHASE IB STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND CLINICAL ACTIVITY OF THE COMBINATION OF RO6870810 AND VENETOCLAX, WITH OR WITHOUT RITUXIMAB, IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA AND/OR HIGH–GRADE B-CELL LYMPHOMA WITH MYC AND/OR BCL2 AND/OR BCL6 GENE REARRANGEMENTS

• IRAS ID

  257257

• Contact name

  Christopher Fox

• Contact email

  christopher.fox2@nuh.nhs.uk

• Sponsor organisation

  F. Hoffmann-La Roche Ltd

• Eudract number

  2017-000357-39

• Clinicaltrials.gov Identifier

  CANC 40388, CRN Number

• Duration of Study in the UK

  2 years, 7 months, 31 days

• Research summary

  Diffuse large B-cell lymphoma(DLBCL)and high-grade B-cell lymphoma with MYC and\nBCL2 and/or BCL6 gene rearrangements(HGBL-DH/TH)are subgroups of non-Hodgkin’s lymphoma(NHL)in adults,with a combined incidence of 50,000 cases in the US and EU.With current treatments more than half of DLBCL patients may be cured,resulting in an overall 5-year survival rate exceeding 55%.Patients with treatment-responsive disease and adequate performance status are candidates for autologous stem cell transplantation(ASCT).Patients with recurrent DLBCL or HGBL-DH/TH following ASCT,or who are ineligible for transplantation,and those with relapsed or refractory(R/R)to first-line therapies who are not candidates for high dose therapy with ASCT,represent a poor prognosis group and a high unmet clinical need.These patients have a prognosis of <6-12months.Those with disease characterised by both MYC and BCL2 gene aberrations have a particularly poor prognosis.\nBromodomains(such as BRD4)are epigenetic regulators that have been identified as transcription co-factors(activators)for several key oncogenic drivers in DLBCL,including MYC and BCL2.Bromodomain and extra-terminal(BET)protein inhibitors such as RO6870810 therefore may offer novel therapeutic options in DLBCL and HGBLDH/TH.\nVenetoclax,a BCL2 inhibitor,has demonstrated single agent responses in relapsed DLBCL.The co-administration of BCL2(venetoclax)and BET(JQ1)inhibitors produced the most potent synergistic effects among combinations tested in DE-DLBCL cell lines and primary patient-derived HGBLDH models.Rituximab,a cornerstone of therapy in DLBCL,has demonstrated efficacy in the relapsed setting and may enhance activity within this combination regimen.\nThis Phase Ib study will explore RO6870810 given with venetoclax, with/without rituximab,in patients with R/R DLBCL and/or HGBL-DH/TH following a first-line regimen containing an anti-CD20 directed agent. \nPart 1 – dose escalation is already underway globally.Part 2 – The dose-expansion part will open once the RDs have been established in Part 1.The UK will take part in part 2.\n134 patients will take part in the study with 80 in part 2.Of these approximately 9 will be from the UK across 4-5 sites.\nThe study is sponsored by F. Hoffman La Roche.\nResearch Summary;Version 1.0(07/11/2018).

• REC name

  Yorkshire & The Humber - Leeds East Research Ethics Committee

• REC reference

  19/YH/0036

• Date of REC Opinion

  12 Mar 2019

• REC opinion

  Further Information Favourable Opinion