a study to evaluate safety, pharmacokinetics, and clinical activity of combination of ro6870810 and venetoclax, with or without rituximab, in participants with relapsed/refractory dlbcl and/or high-grade b-cell lymphoma and/or high grade b-cell lymphoma with myc and/or bcl2 and/or bcl6

Conditions: Diffuse Large B-cell Lymphoma; High-Grade B-cell Lymphoma

Summary: the purpose of this study is to evaluate the safety, tolerability and clinical activity of ro6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (r/r) diffuse large b-cell lymphoma (dlbcl) and/or high-grade b-cell lymphoma with myelocytomatosis oncogene (myc) and/or b-cell lymphoma 2 (bcl2) and/or b-cell lymphoma 6 (bcl6) gene rearrangements (hgbl-dh/th).


Eligibility criteria:
inclusion criteria * cooperative oncology group (ecog) performance status of 0, 1, or 2. * life expectancy \>3 months as per investigator's assessment. * part 1 and part 2 group 1: participantts with diffuse large b-cell lymphoma (dlbcl) relapsed or refractory to ≥ 1 course of chemotherapy including an anti-cd20 monoclonal antibody, and not eligible for autologous stem cell transplantation (asct) (including due to chemorefractory disease). participants with transformed fl are eligible, provided dlbcl or hgbl-dh/th histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. the sponsor retains the option to limit the number of participants enrolled with transformed fl. part 2, group 2: patients identified with de-dlbcl (expression myc ≥40%, bcl2 \> 50%) and or hgbl-dh/th, relapsed or refractory to \>= 1 course of chemotherapy including an anti-cd20 monoclonal antibody, and not eligible for asct (including due to chemorefractory disease). patients with transformed follicular lymphoma (fl) are eligible, provided de-dlbcl and/or hgbl-dh/th histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. the sponsor retains the option to limit the number of participants enrolled with transformed fl. * part 1 and part 2: willing to provide the protocol specified tumor biopsy(ies): at screening a fresh biopsy (if no archival biopsy tissue of less than 3 months prior to treatment and without intercurrent treatment is available); part 2: willing to provide an additional biopsy on cycle 2 day 15 (+ 2 days). * acceptable liver function, as specified below: * total bilirubin ≤ 2 times upper limit of normal (uln). (participants with known gilbert's disease who has serum bilirubin ≤ 3 × uln may be enrolled). * aspartate transaminase (ast; sgot), alanine transaminase (alt; sgpt) ≤ 2.5 × uln, (or ≤ 5 × uln if tumor involvement (liver) is present). * gamma-glutamyl transferase (ggt) alkaline phosphatase ≤ 2.5 × uln. * acceptable renal function, as specified below: • creatinine clearance (crcl) calculated by cockroft-gault formula of ≥ 60 ml/min. * acceptable hematologic status (growth factors cannot be used within the previous 7 days), as specified below: * absolute neutrophil count (anc) ≥ 1000 cells/μl * hemoglobin ≥ 9 g/dl * platelet count ≥ 75,000 (platelets/μl) * uncontrolled symptomatic hypercalcemia. * acceptable coagulation status, as specified below: * prothrombin time (pt) and partial thromboplastin time (ptt) ≤ 1.2 × uln (unless receiving anticoagulation therapy, if receiving anticoagulation therapy, eligibility will be based upon international normalized ratio \[inr\]). * inr ≤ 1.6 (unless receiving anticoagulation therapy). * if receiving warfarin: inr ≤ 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy). * acceptable method of contraception exclusion criteria * 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.