A Study of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus (+) Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Follicular Lymphoma (FL) or Rituximab + CHOP in Participants With Diffuse Large B-Cell Lymphoma (DLBCL)

NCT02596971 | Completed Phase 1 Results

• 2 other identifiers: BO295632015-001364-19
• Study Type: interventional
• Target: 91
• Locations: 3 countries
• Sites: 21

Brief Summary

This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with either obinutuzumab + bendamustine (Atezo-G-benda) or obinutuzumab + CHOP (Atezo-G-CHOP) in participants with FL and atezolizumab + rituximab + chemotherapy (Atezo-R-CHOP) in participants with DLBCL, followed by post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in participants with FL who achieve a complete response (CR) or partial response (PR) at end of induction (EOI) or atezolizumab alone in participants with DLBCL who achieve a CR at EOI.

Conditions

Diffuse Large B-Cell Lymphoma, Lymphoma Follicular

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria

  Primary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to \[\</=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \</=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All PET evaluable 1L FL and 1L DLBCL participants with at least one dose of atezolizumab were included in efficacy population.

  Up to approximately 6 months

• Percentage of Participants With Adverse Events

  An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

  Baseline up to approximately 4 years

Secondary Outcomes (14)

• Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria

  Up to approximately 6 months

• Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria

  Up to approximately 6 months

• Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria

  Up to approximately 6 months

• Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria

  Up to approximately 6 months

• Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria

  Up to approximately 6 months

Study Arms (3)

Atezo-G-Benda (Safety Run-In and Expansion Phases)

EXPERIMENTAL

Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month \[q2m\]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL will receive same treatment regimen as described for safety run-in phase.

Drug: Atezolizumab; Drug: Bendamustine; Drug: Obinutuzumab

Atezo-G-CHOP (Safety Run-In Phase)

EXPERIMENTAL

Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment.

Drug: Atezolizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Obinutuzumab; Drug: Prednisone; Drug: Vincristine

Atezo-R-CHOP (Expansion Phase)

EXPERIMENTAL

Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment.

Drug: Atezolizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Rituximab

Interventions

Atezolizumab DRUG

Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.

Also known as: RO5541267; Tecentriq

Atezo-G-Benda (Safety Run-In and Expansion Phases); Atezo-G-CHOP (Safety Run-In Phase); Atezo-R-CHOP (Expansion Phase)

Bendamustine DRUG

Bendamustine will be administered at a dose of 90 milligrams per square meter (mg/m\^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment.

Atezo-G-Benda (Safety Run-In and Expansion Phases)

Cyclophosphamide DRUG

Cyclophosphamide will be administered at a dose of 750 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Atezo-G-CHOP (Safety Run-In Phase); Atezo-R-CHOP (Expansion Phase)

Doxorubicin DRUG

Doxorubicin will be administered at a dose of 50 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Atezo-G-CHOP (Safety Run-In Phase); Atezo-R-CHOP (Expansion Phase)

Obinutuzumab DRUG

Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.

Also known as: RO5072759

Atezo-G-Benda (Safety Run-In and Expansion Phases); Atezo-G-CHOP (Safety Run-In Phase)

Prednisone DRUG

Prednisone will be administered at a dose of 40 mg/m\^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m\^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).

Atezo-G-CHOP (Safety Run-In Phase); Atezo-R-CHOP (Expansion Phase)

Vincristine DRUG

Vincristine will be administered at a dose of 1.4 mg/m\^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.

Atezo-G-CHOP (Safety Run-In Phase); Atezo-R-CHOP (Expansion Phase)

Rituximab DRUG

Atezo-R-CHOP: Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m\^2 IV on Day 1 of Cycle 1-8, during induction treatment.

Atezo-R-CHOP (Expansion Phase)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment
• For participants enrolled in the expansion phase: lymphoma classified as either previously untreated Grade 1, 2, or 3a FL that requires treatment or previously untreated advanced DLBCL
• Histologically documented cluster of differentiation 20 (CD20) positive lymphoma
• Fluorodeoxyglucose-avid lymphoma
• At least one bi-dimensionally measurable lesion (greater than \[\>\] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
• Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
• For women who are not postmenopausal or surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than \[\<\] 1 percent \[%\] per year during the treatment period and for at least 18 months after the last dose of study treatment for participants in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 12 months after the last dose of study treatment for participants in the Atezo-R-CHOP treatment group
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

You may not qualify if:

• Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's lymphoma (NHL)
• Central nervous system lymphoma or leptomeningeal infiltration
• For participants with DLBCL: preplanned consolidative radiotherapy
• Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
• For participants with relapsed or refractory FL: prior allogeneic or autologous stem cell transplantation, anthracycline therapy, treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of Cycle 1, treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1, radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
• History of solid organ transplantation
• History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab, obinutuzumab, rituximab, or bendamustine formulation, including mannitol
• Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening
• History of progressive multifocal leukoencephalopathy
• Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1
• History of other malignancy, autoimmune disease, or any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results
• Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, or anticipation of a major surgical procedure during the course of the study
• For participants who will be receiving CHOP: left ventricular ejection fraction (LVEF) \<50% by multiple-gated acquisition (MUGA) scan or echocardiogram
• Inadequate hematologic, renal, and liver function (unless due to underlying lymphoma)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (21)

Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, 80012, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University Miami

Miami, Florida, 33136, United States

Location

New York Uni Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oncology Associates of Oregon, P.C.; Willamette Valley Cancer Institute

Springfield, Oregon, 97477, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Oncology

Austin, Texas, 78705, United States

Location

Texas Oncology-Tyler

Irving, Texas, 75063, United States

Location

Concord Repatriation General Hospital; Haematology

Sydney, New South Wales, 2139, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

The Queen Elizabeth Hospital; Haematology/Oncology

Woodville South, South Australia, 5011, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Azienda Ospedaliera S. Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, Emilia-Romagna, 47014, Italy

Location

Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia

Ravenna, Emilia-Romagna, 48100, Italy

Location

Ospedale Infermi di Rimini

Rimini, Emilia-Romagna, 47900, Italy

Location

AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette

Torino, Lazio, 10126, Italy

Location

Asst Papa Giovanni XXIII

Bergamo, Lombardy, 24100, Italy

Location

Azienda Ospedaliera Univ

Florence, Tuscany, 50141, Italy

Location

Related Publications (2)

• Younes A, Burke JM, Cheson BD, Diefenbach CS, Ferrari S, Hahn UH, Hawkes EA, Khan C, Lossos IS, Musuraca G, Tani M, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Sharman JP. Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma. Blood Adv. 2023 Apr 25;7(8):1488-1495. doi: 10.1182/bloodadvances.2022008344.

  PMID: 36287231 DERIVED

• Younes A, Burke JM, Diefenbach C, Ferrari S, Khan C, Sharman JP, Tani M, Ujjani C, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Gilbertson M. Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. Blood Adv. 2022 Oct 25;6(20):5659-5667. doi: 10.1182/bloodadvances.2021006131.

  PMID: 35359000 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

atezolizumab; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; obinutuzumab; Prednisone; Vincristine; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Development of the atezolizumab combination treatment was discontinued as there was insufficient evidence regarding the additive efficacy of this therapy.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: November 3, 2015
• First Posted: November 4, 2015
• Study Start: December 22, 2015
• Primary Completion: April 11, 2018
• Study Completion: May 8, 2020
• Last Updated: May 24, 2021
• Results First Posted: June 13, 2019

Record last verified: 2021-04

Locations

IT (7); AU (5); US (9)