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Completed

NCT Number: NCT02458638

A 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.

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Key information

Conditions

Tumors Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie, Graz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody

Drug

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

Primary outcomes

  1. Non-progression Rate (NPR) at 18 Weeks

    Time frame: At 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 outcomes

  1. NPR at 24 Weeks

    Time frame: At 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.

  2. Overall Response Rate (ORR)

    Time frame: 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.

  3. Percentage of Participants by Best Overall Response (BOR)

    Time frame: 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.

  4. Clinical Benefit Rate (CBR)

    Time frame: 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.

  5. Duration of Objective Response (DOR)

    Time frame: 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.

  6. Progression-Free Survival (PFS)

    Time frame: 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.

  7. Time to Progression (TTP)

    Time frame: 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.

  8. Overall Survival (OS)

    Time frame: 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.

  9. Number of Participants With Adverse Events

    Time frame: Baseline 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.

  10. Treatment Duration of Atezolizumab

    Time frame: Baseline up to approximately 4.5 years

  11. Mean Number of Doses of Atezolizumab

    Time frame: Baseline up to approximately 4.5 years

  12. Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab

    Time frame: Baseline up to 4.5 years

  13. Serum Concentration of Atezolizumab

    Time frame: 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

  14. Percentage of Participants by Best Overall Response Based on Modified RECIST v1.1 (mBOR)

    Time frame: 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.

  15. ORR Based on Modified RECIST v1.1

    Time frame: 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. 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.

  16. CBR Based on Modified RECIST v1.1

    Time frame: 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. 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.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

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

Important dates

Study start
2015
Primary completion
2018
Study completion
2020
First posted
Jun 1, 2015
Registry last updated
Jun 4, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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