a study evaluating the safety, efficacy and pharmacokinetics of venetoclax in combination with polatuzumab vedotin plus rituximab (r) and cyclophosphamide, doxorubicin, prednisone (chp) in participants with untreated bcl-2 immunohistochemistry (ihc)-positive diffuse large b-cell lymphoma (dlbcl)

Conditions: Lymphoma, Large B-Cell, Diffuse

Summary: this phase ib, open-label, multicenter study evaluates the safety, efficacy, and pharmacokinetics of venetoclax in combination with pola + r-chp in previously untreated participants with bcl-2 ihc-positive dlbcl. approximately 50 participants will be enrolled in this study in five consecutive cohorts each consisting of approximately 10 participants.


Eligibility criteria:
inclusion criteria: * previously untreated participants with cd20-positive dlbcl. * bcl-2 protein overexpression by ihc, as assessed by local testing. * eastern cooperative oncology group (ecog) performance status of 0, 1, or 2. * international prognostic index (ipi) 2-5. * life expectancy of more than 6 months. * left ventricular ejection fraction (lvef) ≥ 50%, as determined on cardiac multiple-gated acquisition (muga) scan or cardiac echocardiogram (echo). * availability of archival or freshly collected tumor tissue prior to study enrollment. * at least one bi-dimensionally fluorodeoxyglucose-avid measurable lymphoma lesion on pet/ct scan, defined as \> 1.5 cm in its longest dimension on ct scan. * adequate hematopoietic function. * for women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs. * for men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm. exclusion criteria: * current diagnosis of unclassifiable b-cell lymphoma. * prior treatment for indolent lymphoma. * current grade \> 1 peripheral neuropathy. * prior organ transplantation. * prior use of any monoclonal antibody within 3 months and any investigational therapy within 28 days prior to the start of cycle 1. * vaccination with live vaccines within 28 days prior to the start of cycle 1. * prior therapy for dlbcl and high-grade b-cell lymphoma (hgbcl) with the exception of palliative, short-term treatment with corticosteroids. * recent major surgery (within 6 weeks prior to the start of day 1 of cycle 1), other than for diagnosis. * history of other cancers within 2 years prior to screening. * any active infection that, in the opinion of the investigator, would impact participant safety within 7 days prior to day 1 of cycle 1. * serious infection requiring oral or iv antibiotics within 4 weeks prior to day 1 of cycle 1. * any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study. * positive test for hepatitis b/c viruses (hbv/hcv) and human t-cell leukemia virus (htlv)-1. * known infection with hiv. * history of progressive multifocal leukoencephalopathy. * suspected active or latent tuberculosis. * clinically significant history of liver disease, including viral or other hepatitis or cirrhosis. * substance abuse, including non-prescription drug and alcohol dependence, within 12 months prior to screening. * pregnant or breastfeeding, or intending to become pregnant during the study within 6 months after the final dose of venetoclax, 9 months after the final dose of polatuzumab vedotin, or 12 months after the final dose of rituximab. * history or presence of an abnormal ecg that is clinically significant in the investigator's opinion. * malabsorption syndrome or other condition that would interfere with enteral absorption. * blood transfusion within 14 days prior to screening.