MedPath

A Study of Atezolizumab in Advanced Solid Tumors

Registration Number
NCT02458638
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
474
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
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AtezolizumabAtezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibodyThe 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.
Primary Outcome Measures
NameTimeMethod
Non-progression Rate (NPR) at 18 WeeksAt Week 18

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.

Secondary Outcome Measures
NameTimeMethod
Time to Progression (TTP)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), 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.

Overall Survival (OS)Baseline until death due to any cause (up to 4.5 years)

OS was defined as the time from the first day of study treatment to death from any cause.

Number of Participants With Adverse EventsBaseline up to 4.5 years

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.

Treatment Duration of AtezolizumabBaseline up to approximately 4.5 years
Mean Number of Doses of AtezolizumabBaseline up to approximately 4.5 years
Percentage of Participants With Anti-drug Antibodies (ADAs) to AtezolizumabBaseline up to 4.5 years
NPR at 24 WeeksAt Week 24

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.

Overall Response Rate (ORR)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 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.

Percentage of Participants by Best Overall Response (BOR)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)

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.

Clinical Benefit Rate (CBR)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 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.

Duration of Objective Response (DOR)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)

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.

Progression-Free Survival (PFS)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)

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.

Serum Concentration of AtezolizumabPredose 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)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)

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.

ORR Based on Modified RECIST v1.1Baseline 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)

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.

CBR Based on Modified RECIST v1.1Baseline 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)

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.

Trial Locations

Locations (48)

St Vincent'S Uni Hospital; Medical Oncology

🇮🇪

Dublin, Ireland

Oslo Universitetssykehus HF; Radiumhospitalet

🇳🇴

Oslo, Norway

Freiburger Spital; Onkologie

🇨🇭

Fribourg, Switzerland

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Chemotherapie & Infektionskrankhei

🇦🇹

Wien, Austria

Helsinki University Central Hospital; Dept of Oncology

🇫🇮

Helsinki, Finland

The Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen

🇩🇪

Heidelberg, Germany

Institut Gustave Roussy

🇫🇷

Villejuif, France

Uniklinik-Eppendorf; Zentren F. Innere Medizin-Klinik U. Poliklinik

🇩🇪

Hamburg, Germany

Fondazione IRCCS Istituto Nazionale dei Tumori

🇮🇹

Milano, Lombardia, Italy

Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie

🇩🇪

Trier, Germany

Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii

🇵🇱

Gdańsk, Poland

Aarhus Universitetshospital; Kræftafdelingen

🇩🇰

Aarhus N, Denmark

Southampton General Hospital; Medical Oncology

🇬🇧

Southampton, United Kingdom

Memorial Sloan Kettering

🇺🇸

New York, New York, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Sarah Cannon Cancer Center and Research Institute

🇺🇸

Nashville, Tennessee, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie

🇦🇹

Graz, Austria

INCA 1- Instituto Nacional de Câncer X

🇧🇷

Rio de Janeiro, RJ, Brazil

Hospital das Clinicas - UFRGS

🇧🇷

Porto Alegre, RS, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, SP, Brazil

BCCA-Vancouver Cancer Centre

🇨🇦

Vancouver, British Columbia, Canada

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

🇨🇦

Toronto, Ontario, Canada

Herlev Hospital; Afdeling for Kræftbehandling

🇩🇰

Herlev, Denmark

Odense Universitetshospital, Onkologisk Afdeling, Klinisk Forsknings Enhed

🇩🇰

Odense C, Denmark

Institut Bergonie

🇫🇷

Bordeaux, France

Centre Leon Berard; Departement Oncologie Medicale

🇫🇷

Lyon, France

Hopital Saint Louis, Service D Oncologie Medicale

🇫🇷

Paris, France

St James' Hospital; Cancer Clinical Trials Office

🇮🇪

Dublin, Ireland

Istituto Nazionale Tumori Fondazione G. Pascale

🇮🇹

Napoli, Campania, Italy

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

🇮🇹

Siena, Toscana, Italy

Antoni van Leeuwenhoek Ziekenhuis

🇳🇱

Amsterdam, Netherlands

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Haukeland Universitetssjukehus; Klinisk forskningspost

🇳🇴

Bergen, Norway

Universitair Medisch Centrum Utrecht

🇳🇱

Utrecht, Netherlands

Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy

🇷🇺

Moscow, Russian Federation

Centrum Onkologii w Bydgoszczy

🇵🇱

Bydgoszcz, Poland

Clinica Universitaria de Navarra; Servicio de Oncologia

🇪🇸

Pamplona, Navarra, Spain

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

🇷🇺

Saint-Petersburg, Russian Federation

Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Now. Tkanek Miekkich,Kosci i Czer.

🇵🇱

Warszawa, Poland

Hospital Univ Vall d'Hebron; Servicio de Oncologia

🇪🇸

Barcelona, Spain

Trakya University Medical Faculty

🇹🇷

Edirne, Turkey

Kantonsspital St. Gallen; Onkologie/Hämatologie

🇨🇭

St. Gallen, Switzerland

Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology

🇹🇷

Istanbul, Turkey

Prof. Dr. Cemil Tascioglu City Hospital; Med Onc

🇹🇷

Istanbul, Turkey

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

🇹🇷

Sihhiye/Ankara, Turkey

Clatterbridge Cancer Centre

🇬🇧

Bebington, United Kingdom

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