NP39461: This phase I trial is evaluating the safety of a new drug (RO6870810) in combination with a chemotherapy and/or an immunotherapy for patients with Diffuse Large B-Cell LymphomaOpen-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 (DLBCL) and/or High-Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 Gene Rearrangements

Exclusion

• Current central nervous system (CNS) lymphoma or leptomeningeal infiltration.
• New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, within the past 6 months, unstable arrhythmia, or known pericardial disease.
• Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome.
• Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator would preclude safe participation in the study.
• Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
• Clinically important respiratory impairment
• Grade ≥ 3 sensory or motor neuropathy.
• Any Grade >1 (according to the NCI CTCAE 4.03) adverse reaction unresolved from previous treatments and not readily managed and controlled with supportive care.
• Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
• History of progressive multifocal leukoencephalopathy (PML).
• History of other malignancy within 2 years prior to screening, except for ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score ≤ 7) not requiring treatment or appropriately treated Stage I uterine cancer.
• Completion of ASCT within 100 days prior to Day 1 of Cycle1.

• Prior standard or investigational anti-cancer therapy, as specified below:

  • Radio-immunoconjugate 4 weeks or 5 half-lives, whichever is longer prior to Day 1 of Cycle 1.
  • Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 3 weeks prior to Day 1 of Cycle 1.
  • Radiotherapy, chemotherapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1.
  • CAR T-cell therapy 30 days prior to Day 1 of Cycle 1.
• History of major solid organ transplant (i.e., heart, lungs, liver and kidney).
• History of an allogeneic bone marrow transplant.
• Major surgical procedure within 28 days prior to Day 1 of Cycle 1.

• Treatment with systemic corticosteroids ≥ 20 mg/day prednisone or equivalent, for non-lymphoma treatment reasons. For lower acceptable doses, documentation of a stable dose for at least 4 weeks prior to Day 1 of Cycle 1 is required.

  18. Treatment with strong to moderate CYP3A inhibitors or moderate CYP3A inducers within 7 days prior to the first dose of study treatment.

• Treatment with strong CYP3A inducers within 14 days prior to the first dose of study treatment of RO6870810/venetoclax.
• Consumption of grapefruits, grapefruit products, Seville oranges (including marmalade that contains Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax.
• Participants who are currently receiving any other investigational agent ((other than anti-cancer therapy as specified in exclusion criteria number 13) or have received an investigational agent within 30 days or 5 half-lives prior to Day 1 of Cycle 1, whichever is longer.
• Prior treatment with small molecule bromodomain and extra terminal (BET) family inhibitor.
• Known to be human immunodeficiency virus (HIV) positive.
• Presence of positive test results for hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HcAb) (for participants receiving regimen including rituximab)
• Pregnant or breastfeeding female.
• Significant allergy to a biological pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the participant.
• Uncontrolled cancer pain. Participants requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrollment.
• History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies (for participants receiving regimen including rituximab).
• Known sensitivity or allergy to murine products or any component of RO6870810, venetoclax, or rituximab.