Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the BO42203 study.

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.

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.

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).