A Safety and Pharmacology Study of Atezolizumab (MPDL3280A) Administered With Obinutuzumab or Tazemetostat in Participants With Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma

NCT ID: NCT02220842

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-18
• Study Completion Date: 2020-01-21

Brief Summary

This open-label, multicenter, global study is designed to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of intravenous atezolizumab (MPDL3280A) and obinutuzumab in participants with refractory or relapsed follicular lymphoma (FL) or atezolizumab and obinutuzumab or tazemetostat administered in participants with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). The anticipated duration of this study is approximately 4.5 years.

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab

Relapsed/refractory FL and DLBCL participants will receive obinutuzumab alone on Days 1, 8, and 15 of Cycle 1 (Cycle length = 21 days), followed by atezolizumab and obinutuzumab on Day 1 of Cycles 2-8, and then atezolizumab alone on Day 1 of Cycle 9 and every cycle thereafter until unacceptable toxicities or disease progression.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

Obinutuzumab

Intervention Type: DRUG

During safety evaluation stage, obinutuzumab will be administered as 1000 mg IV infusion. During expansion stage, obinutuzumab will be administered as either 1000 mg IV infusion or at dose decided from safety evaluation stage.

Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab

Relapsed/refractory FL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

Obinutuzumab

Intervention Type: DRUG

During safety evaluation stage, obinutuzumab will be administered as 1000 mg IV infusion. During expansion stage, obinutuzumab will be administered as either 1000 mg IV infusion or at dose decided from safety evaluation stage.

Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab

Relapsed/refractory DLBCL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

Tazemetostat

Intervention Type: DRUG

Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.

Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat

Relapsed/refractory DLBCL participants will receive atezolizumab (on Day 1) and tazemetostat (on Days 1-21) of each 21-day cycle until unacceptable toxicities or disease progression.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

Tazemetostat

Intervention Type: DRUG

Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.

Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat

Relapsed/refractory DLBCL participants will receive atezolizumab and tazemetostat as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

Tazemetostat

Intervention Type: DRUG

Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.

Interventions

Atezolizumab

During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

Intervention Type: DRUG

Obinutuzumab

During safety evaluation stage, obinutuzumab will be administered as 1000 mg IV infusion. During expansion stage, obinutuzumab will be administered as either 1000 mg IV infusion or at dose decided from safety evaluation stage.

Intervention Type: DRUG

Tazemetostat

Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; EPZ6438

Eligibility Criteria

Inclusion Criteria

• Histologically documented, CD20-positive, relapsed or refractory (defined as having relapsed within 6 months to the previous treatment) FL or DLBCL (including primary mediastinal large B-cell lymphoma [PMLBCL])
• Bone marrow biopsy at screening (unless it was performed within 3 months prior to screening)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Life expectancy greater than or equal to (>=) 12 weeks
• Has a QT interval corrected by Fridericia's formula (QTcF) less than or equal to (<=) 480 milliseconds (msec)
• At least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest diameter by computed tomography (CT) scan or MRI, as defined by the Lugano Classification
• Adequate hematologic and end-organ function
• Archival tumor tissue
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of atezolizumab or 18 months after the last dose of obinutuzumab, whichever is longer
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); participants with indwelling catheters are eligible
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homolog 2 (EZH2)
• Regular treatment with corticosteroids within the 2 or 4 weeks prior to the start of Cycle 1, unless administered for indications other than non-Hodgkin's lymphoma at a dose equivalent to < 30 mg/day prednisone/prednisolone
• Pregnant and lactating women
• History of autoimmune disease
• Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed
• Positive test for Human Immunodeficiency Virus (HIV)
• History of chronic hepatitis B infection or positive test results for active or chronic hepatitis B or hepatitis C
• Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
• Hypersensitivity or prior treatment with obinutuzumab
• Fludarabine or Campath within 12 months prior to study entry
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including but not limited to interferon, interleukin-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
• Treatment with systemic immunosuppressive medications, including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents within 2 weeks prior to Cycle 1, Day 1; inhaled corticosteroids and mineralocorticoids are allowed
• Participants with active tuberculosis (TB) will be excluded from the clinical trial

Exclusion Criteria

• Known central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation from an indolent lymphoma to a high-grade or DLBCL

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope National Medical Center

Duarte, California, United States

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Sloan Kettering Cancer Center

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

UW- Fred Hutchinson Cancer Center

Seattle, Washington, United States

Hopital Claude Huriez - CHU Lille; Service des maladies du sang

Lille, , France

Hopital Saint Eloi

Montpellier, , France

Hôpital Saint-Louis

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Institut Gustave Roussy

Villejuif, , France

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Barts Hospital

London, , United Kingdom

Countries

United States; France; Germany; Italy; United Kingdom

References

Palomba ML, Cartron G, Popplewell L, Ribrag V, Westin J, Huw LY, Agarwal S, Shivhare M, Hong WJ, Raval A, Chang AC, Penuel E, Morschhauser F. Combination of Atezolizumab and Tazemetostat in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results From a Phase Ib Study. Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):504-512. doi: 10.1016/j.clml.2021.12.014. Epub 2021 Dec 24.

Reference Type: DERIVED

PMID: 35151584 (View on PubMed)

Palomba ML, Till BG, Park SI, Morschhauser F, Cartron G, Marks R, Shivhare M, Hong WJ, Raval A, Chang AC, Penuel E, Popplewell LL. Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):e443-e451. doi: 10.1016/j.clml.2021.12.010. Epub 2021 Dec 24.

Reference Type: DERIVED

PMID: 35031227 (View on PubMed)

Other Identifiers

2014-001812-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29383

Identifier Type: -

Identifier Source: org_study_id