A Study of Atezolizumab in Advanced Solid Tumors

An Open-Label, Multicohort, Phase II Study of Atezolizumab in Advanced Solid Tumors

The primary efficacy objective for this study is to evaluate non-progression rate (NPR) at 18 weeks in participants with advanced solid tumors treated with atezolizumab, defined as the percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1, or according to disease-specific criteria for prostate cancer and malignant pleural mesothelioma.

Study Overview

• Status: Completed
• Conditions: Tumors
• Intervention / Treatment: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody

• Study Type: Interventional
• Enrollment (Actual): 474
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Chemotherapie & Infektionskrankhei
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20231-050
      • INCA 1- Instituto Nacional de Câncer X
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital; Kræftafdelingen
  • Herlev, Denmark, 2730
    • Herlev Hospital; Afdeling for Kræftbehandling
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling, Klinisk Forsknings Enhed
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital; Dept of Oncology
• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Lyon, France, 69373
    • Centre Leon Berard; Departement Oncologie Medicale
  • Paris, France, 75475
    • Hopital Saint Louis, Service D Oncologie Medicale
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Hamburg, Germany, 20246
    • Uniklinik-Eppendorf; Zentren F. Innere Medizin-Klinik U. Poliklinik
  • Heidelberg, Germany, 69120
    • Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
  • Trier, Germany, 54290
    • Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
• Ireland
  • Dublin, Ireland, 4
    • St Vincent'S Uni Hospital; Medical Oncology
  • Dublin, Ireland
    • St James' Hospital; Cancer Clinical Trials Office
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Fondazione G. Pascale
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Fondazione Irccs Istituto Nazionale Dei Tumori
  • Toscana
    • Siena, Toscana, Italy, 53100
      • Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Antoni van Leeuwenhoek Ziekenhuis
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssjukehus; Klinisk forskningspost
  • Oslo, Norway, 0310
    • Oslo Universitetssykehus HF; Radiumhospitalet
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii w Bydgoszczy
  • Gdańsk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Now. Tkanek Miekkich,Kosci i Czer.
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
  • Saint-Petersburg, Russian Federation, 197758
    • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oncologia
• Switzerland
  • Fribourg, Switzerland, 1708
    • Freiburger Spital; Onkologie
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen; Onkologie/Hämatologie
• Turkey
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey, 34300
    • Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
  • Istanbul, Turkey, 34384
    • Prof. Dr. Cemil Tascioglu City Hospital; Med Onc
  • Sihhiye/Ankara, Turkey, 06230
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• United Kingdom
  • Bebington, United Kingdom, CH63 4JY
    • Clatterbridge Cancer Centre
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital; Medical Oncology
• United States
  • New York
    • New York, New York, United States, 10027
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center and Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressive disease at study entry, and have received at least one line of prior systemic therapy or for which no alternative therapy to prolong survival exists
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or in freshly cut and unstained slides (exceptional cases) with an associated pathology report for central testing
• Measurable disease as defined by RECIST v1.1 or disease-specific criteria for prostate cancer and malignant pleural mesothelioma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Negative serum pregnancy test result within 14 days prior to study drug among women of childbearing potential
• Life expectancy > 3 months

Exclusion Criteria:

• Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1 except those with a negligible risk of metastasis or death
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures >/=1 time per month
• History of asymptomatic or symptomatic central nervous system (CNS) metastasis
• Leptomeningeal disease
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated but without evidence that disease has been clinically stable for >/=2 weeks prior to Day 1 of Cycle 1
• Pregnant and lactating women
• Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1
• Severe infection within 4 weeks prior to Day 1 of Cycle 1
• Oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
• History of autoimmune disease except treated/stable hypothyroidism, Type 1 diabetes mellitus, and protocol-specified dermatologic conditions
• Active tuberculosis
• Signs or symptoms of infection within 2 weeks prior to Day 1 of Cycle 1
• Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, or anti-programmed cell death-1 (PD-1) or anti-PD-L1 therapeutic antibodies
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Day 1 of Cycle 1, or anticipated requirement for systemic immunosuppressive medications during the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab; The dose of atezolizumab in this study will be 1200 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.	Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Atezolizumab will be given as IV infusion over 60 minutes on Day 1 of Cycle 1, then over 30 minutes (as tolerated) on Day 1 of each subsequent 3-week cycle.; Other Names: Tecentriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-progression Rate (NPR) at 18 Weeks	NPR was defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 or for malignant pleural mesothelioma according to Malignant Pleural Mesothelioma Response Evaluation Criteria. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions in the absence of CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions. For prostate cancer according to Prostate Response Evaluation Criteria. CR: PSA <5 ng/ml measured twice at least 3 weeks apart or PSA response: PSA < 50% of the PSA reference value occurring at any time after treatment was initiated.	At Week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NPR at 24 Weeks	NPR was defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 or for malignant pleural mesothelioma according to Malignant Pleural Mesothelioma Response Evaluation Criteria. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions in the absence of CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions. For prostate cancer according to Prostate Response Evaluation Criteria. CR: PSA <5 ng/ml measured twice at least 3 weeks apart or PSA response: PSA < 50% of the PSA reference value occurring at any time after treatment was initiated.	At Week 24
Overall Response Rate (ORR)	ORR was defined as the percentage of participants with CR or PR as assessed by the investigator using RECIST v1.1 or Malignant Pleural Mesothelioma Response Evaluation Criteria. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR. For prostate cancer according to Prostate Response Evaluation Criteria. CR: PSA <5 ng/ml measured twice at least 3 weeks apart or PSA response: PSA < 50% of the PSA reference value occurring at any time after treatment was initiated.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Percentage of Participants by Best Overall Response (BOR)	BOR was based on RECIST v1.1, Malignant Pleural Mesothelioma Response Evaluation Criteria or Prostate Response Evaluation Criteria. For an individual participant BOR was obtained as follows: 1) CR: overall tumor response assessment of CR at 2 consecutive visits at least 28 days apart. 2) PR: overall tumor response assessment of PR or CR at 2 consecutive visits at least 28 days apart without being a CR. 3) SD: overall tumor response assessment of SD, PR, or CR at one or more visits at least 42 days after start of study treatment, but was not a confirmed CR or PR. 4) PD: an overall tumor response assessment of PD at any visit, and did not meet the criteria for a BOR of CR, PR or SD. 5) Missing: an assessment of SD, PR or CR in the first 42 days after start of study treatment and no further tumor assessments thereafter.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants with CR, PR, or SD according to RECIST v1.1, Malignant Pleural Mesothelioma Response Evaluation Criteria or Prostate Response Evaluation Criteria lasting for >/=6 weeks. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions in the absence of CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions. For prostate cancer: CR: PSA <5 ng/ml measured twice at least 3 weeks apart or PSA response: PSA < 50% of the PSA reference value occurring at any time after treatment was initiated.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Duration of Objective Response (DOR)	DOR, based on RECIST v1.1, was defined as the time from the first occurrence of a documented objective response (CR or PR) to the time of progression or death from any cause, whichever occurred first. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions in the absence of CR. PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions. As pre-specified in the Statistical Analysis Plan (SAP) DOR was not analyzed if there were less than 4 participants available for the analysis.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Progression-Free Survival (PFS)	PFS, based on RECIST v1.1, was defined as the time from the first day of study treatment to the first occurrence of disease progression or death from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Time to Progression (TTP)	Time to progression (TTP), based on RECIST v1.1, was defined as time from the first day of study treatment to the first occurrence of progressive disease or death due to disease progression, whichever occurred first. PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
Overall Survival (OS)	OS was defined as the time from the first day of study treatment to death from any cause.	Baseline until death due to any cause (up to 4.5 years)
Number of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a subject 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 4.5 years
Treatment Duration of Atezolizumab		Baseline up to approximately 4.5 years
Mean Number of Doses of Atezolizumab		Baseline up to approximately 4.5 years
Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab		Baseline up to 4.5 years
Serum Concentration of Atezolizumab		Predose and postdose on Day 1 of Cycle 1, predose on Day 1 of Cycles 2, 3, 4, 8 (cycle length = 21 days), and every 8 cycles until treatment discontinuation; at follow up (approximately 120 days after last dose) up to approximately 4.5 years
Percentage of Participants by Best Overall Response Based on Modified RECIST v1.1 (mBOR)	Modified RECIST was based on the following: 1) New measurable lesions were added into the total tumor burden and followed; 2) Non-target lesions contributed only in the assessment of a CR; 3) Radiographic progression was determined only on the basis of measurable disease; had to be confirmed by a consecutive assessment =/>4 weeks from the date first documented. mBOR: 1) CR: overall tumor response assessment of CR at 2 consecutive visits at least 28 days apart. 2) PR: overall tumor response assessment of PR/CR at 2 consecutive visits at least 28 days apart without being a CR. 3) SD: overall tumor response assessment of SD/PR/CR at one or more visits at least 42 days after start of study treatment, but was not a confirmed CR or PR. 4) PD: an overall tumor response assessment of PD at any visit, and did not meet the criteria for a BOR of CR, PR or SD. 5) Missing: an assessment of SD, PR or CR in the first 42 days after start of study treatment and no further tumor assessments thereafter.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
ORR Based on Modified RECIST v1.1	Modified RECIST was based on the following: 1) New measurable lesions were added into the total tumor burden and followed; 2) Non-target lesions contributed only in the assessment of a CR; 3) Radiographic progression was determined only on the basis of measurable disease; had to be confirmed by a consecutive assessment =/>4 weeks from the date first documented. ORR was defined as the percentage of participants with CR or PR. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)
CBR Based on Modified RECIST v1.1	Modified RECIST was based on the following: 1) New measurable lesions were added into the total tumor burden and followed; 2) Non-target lesions contributed only in the assessment of a CR; 3) Radiographic progression was determined only on the basis of measurable disease; had to be confirmed by a consecutive assessment =/>4 weeks from the date first documented. CBR was defined as the percentage of participants with CR, PR, or SD lasting for >/=6 weeks. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions in the absence of CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions.	Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Tabernero J, Andre F, Blay JY, Bustillos A, Fear S, Ganta S, Jaeger D, Maio M, Mileshkin L, Melero I. Phase II multicohort study of atezolizumab monotherapy in multiple advanced solid cancers. ESMO Open. 2022 Apr;7(2):100419. doi: 10.1016/j.esmoop.2022.100419. Epub 2022 Mar 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2015
• Primary Completion (Actual): April 4, 2018
• Study Completion (Actual): July 28, 2020

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: May 28, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Actual): June 4, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Atezolizumab
• Other Study ID Numbers: MO29518; 2015-000269-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO