A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma

NCT01984242 | Completed Phase 2 Results

• 2 other identifiers: WO290742013-003167-58
• Study Type: interventional
• Target: 305
• Locations: 9 countries
• Sites: 45

Brief Summary

This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population

  Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population

  PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population

  PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population

  PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Secondary Outcomes (43)

• Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

• Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature

  From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)

Other Outcomes (1)

• EuroQoL 5 Dimension (EQ-5D) Questionnaire Score

  Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks)

Study Arms (3)

Atezolizumab and Bevacizumab

EXPERIMENTAL

Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Drug: Bevacizumab

Atezolizumab

EXPERIMENTAL

Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union \[EU\] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Drug: Bevacizumab

Sunitinib

ACTIVE COMPARATOR

Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody; Drug: Bevacizumab; Drug: Sunitinib

Interventions

Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody DRUG

Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.

Also known as: Tecentriq, MPDL3280A, RO5541267

Atezolizumab; Atezolizumab and Bevacizumab; Sunitinib

Bevacizumab DRUG

Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.

Also known as: Avastin

Atezolizumab; Atezolizumab and Bevacizumab; Sunitinib

Sunitinib DRUG

Sunitinib will be administered according to the dosage schedule mentioned in the arm description.

Also known as: Sutent

Sunitinib

Eligibility Criteria

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

You may qualify if:

• Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting
• Measurable disease, as defined by RECIST v1.1
• Karnofsky performance score greater than or equal to (\>/=) 70
• Adequate hematologic and end-organ function as defined by protocol
• Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol

You may not qualify if:

• Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control
• Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled hypercalcemia or symptomatic hypercalcemia
• Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome
• Life expectancy of less than (\<) 12 weeks
• Pregnant and lactating women
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease
• Prior allogeneic stem cell or solid organ transplant
• Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
• Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
• Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (45)

HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, 85258, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UCLA

Los Angeles, California, 90024, United States

Location

University of California

San Francisco, California, 94158, United States

Location

Univ Colorado Health Sci Ctr

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Ctr - Denver (Williams)

Denver, Colorado, 80218, United States

Location

Yale Uni School of Medicine; Section of Medical Oncology

New Haven, Connecticut, 06510-3289, United States

Location

Georgetown U; Lombardi Comp Can

Washington D.C., District of Columbia, 20016-1468, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Florida Cancer Specialist, North Region

St. Petersburg, Florida, 33705, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Inst.

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute.

Detroit, Michigan, 48201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

Memorial Sloan-Kettering

New York, New York, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic Foundation; Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Oncology Associates of Oregon, P.C

Eugene, Oregon, 97401, United States

Location

Northwest Cancer Specialists, P.C.

Tigard, Oregon, 97223, United States

Location

Tennessee Oncology PLLC - Nashville (20th Ave)

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232-7610, United States

Location

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Fakultni nemocnice Olomouc

Olomouc, 775 20, Czechia

Location

Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale

Paris, 75908, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, 94805, France

Location

Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

Hanover, 30625, Germany

Location

Klinikum d.Universität München Campus Großhadern

München, 81377, Germany

Location

Klinikum rechts der Isar der TU München; Klinikapotheke

München, 81675, Germany

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, 20133, Italy

Location

Medical Oncology, Arezzo

Arezzo, Tuscany, 52100, Italy

Location

Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica

Siena, Tuscany, 53100, Italy

Location

Centrum Med. Ostrobramska NZOZ Magodent

Warsaw, 04-125, Poland

Location

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, 400015, Romania

Location

Medisprof SRL

Cluj-Napoca, 400058, Romania

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department

Barcelona, 08036, Spain

Location

Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal

Madrid, 28050, Spain

Location

Barts and the London NHS Trust.

London, EC1A 7BE, United Kingdom

Location

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

Location

Christie Hospital Nhs Trust; Medical Oncology

Manchester, M2O 4BX, United Kingdom

Location

Related Publications (2)

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

• Pal SK, McDermott DF, Atkins MB, Escudier B, Rini BI, Motzer RJ, Fong L, Joseph RW, Oudard S, Ravaud A, Bracarda S, Suarez C, Lam ET, Choueiri TK, Ding B, Quach C, Hashimoto K, Schiff C, Piault-Louis E, Powles T. Patient-reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma. BJU Int. 2020 Jul;126(1):73-82. doi: 10.1111/bju.15058. Epub 2020 Apr 24.

  PMID: 32233107 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

atezolizumab; Bevacizumab; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 14, 2013
• Study Start: January 8, 2014
• Primary Completion: October 17, 2016
• Study Completion: January 8, 2019
• Last Updated: December 23, 2019
• Results First Posted: December 21, 2017

Record last verified: 2019-12

Locations

IT (3); GB (3); CZ (1); DE (3); ES (4); US (25); RO (2); PL (1); FR (3)