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

NCT02220842 | Completed Phase 1

• 2 other identifiers: GO293832014-001812-21
• Study Type: interventional
• Target: 96
• Locations: 5 countries
• Sites: 15

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Dose Limiting Toxicities (DLTs)

  21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)

• Recommended Phase 2 Dose (RP2D) of Atezolizumab

  21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)

Secondary Outcomes (12)

• Obinutuzumab Minimum Serum Concentration (Cmin)

  Preinfusion (hour 0) on Day 1, 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)

• Percentage of Participants With Adverse Events (AEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

  Baseline up to approximately 4.5 years

• Percentage of Participants With Anti-therapeutic Antibody Response to Atezolizumab and Obinutuzumab

  Baseline up to approximately 4.5 years

• Atezolizumab Maximum Serum Concentration (Cmax)

  Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)

• Atezolizumab Minimum Serum Concentration (Cmin)

  Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)

Study Arms (5)

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

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Obinutuzumab

Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Obinutuzumab

Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tazemetostat

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

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tazemetostat

Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tazemetostat

Interventions

Atezolizumab 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.

Also known as: Tecentriq

Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab; Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab; Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab; Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat; Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat

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

Tazemetostat DRUG

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

Also known as: EPZ6438

Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab; Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat; Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (15)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46805, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Sloan Kettering Cancer Center

New York, New York, 10065-6007, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UW- Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

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

Lille, 59037, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

Location

Barts Hospital

London, E1 2EF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35151584 DERIVED

• 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.

  PMID: 35031227 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

atezolizumab; obinutuzumab; tazemetostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 20, 2014
• Study Start: December 18, 2014
• Primary Completion: January 21, 2020
• Study Completion: January 21, 2020
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

IT (1); US (7); DE (1); FR (5); GB (1)