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)

• Status: Recruiting
• Trial end date: 2025-02-05
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Cyclophosphamide; Doxorubicin; Prednisone; Rituximab; Venetoclax

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 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.