A Phase Ib Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Venetoclax in Combination With Polatuzumab Vedotin Plus Rituximab (R) and Cyclophosphamide, Doxorubicin, Prednisone (CHP) in Patients With Untreated BCL-2 Immunohistochemistry (IHC)-Positive Diffuse Large B-Cell Lymphoma

BO42203

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.

2021-07-02

2024-06-19

2025-02-12

Active (not recruiting)

Early phase I

50

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 50, 'type': 'ESTIMATED'}}

2024-02-28