CClinicalTrials.gg
TerminatedNCT03452137IMvoke010Updated Oct 9, 2024Results posted

A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck

A Phase 3 interventional study of Atezolizumab and Placebo in Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN), sponsored by Hoffmann-La Roche. Terminated at 135 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-09.

Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment

Why this study was terminated
Decision to terminate the study as its primary endpoint of investigator-assessed event free survival (INV-EFS) was not met at its final EFS analysis. No new safety signals were identified.
Phase
Phase 3
Study type
Interventional
Enrollment
406
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study will evaluate the efficacy and safety of atezolizumab compared with placebo as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (SCCHN)

02

Conditions studied

  • Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histologically or cytologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN)
  • Human Papilloma Virus (HPV) status
  • Completed definitive local therapy
  • Absence of metastatic disease as documented by radiographic scans
  • Adequate hematologic and end-organ function
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the last dose of study treatment. Women must refrain from donating eggs during this same period.
  • Confirmed response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) to definitive local therapy documented by CT with contrast or MRI with contract to head and neck region done >= 8 weeks after completion of definitive local therapy and within 28 days prior to initiation of study drug.

Exclusion criteria

Exclusion Criteria:

  • Patients who have received surgery alone or radiotherapy alone as definitive local therapy
  • Squamous cell carcinoma of the nasopharynx or paranasal sinuses or non-squamous histology
  • Evidence of disease progression or metastatic disease during or following definitive local therapy documented in post-definitive local therapy screening scans
  • Uncontrolled or symptomatic hypercalcemia
  • Active or history of autoimmune disease or immune deficiency
  • Active tuberculosis
  • Significant cardiovascular disease
  • History of malignancy, including prior SCCHN primary tumors within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Prior allogeneic stem cell or solid organ transplantation
  • Current treatment with anti-viral therapy for Hepatitis B Virus (HBV)
  • Treatment with systemic immunostimulatory agents
  • Treatment with systemic immunosuppressive medication
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment
  • Patients who have received a non-FDA or non-EMA approved anti-EGFR agent or any other non-FDA or non-EMA, approved agent as part of definitive local therapy, unless the unapproved agent was given in addition to an approved agent
  • Any systemic therapies after permitted definitive local therapies
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
406 participants (actual)

Study arms

  • Active comparator
    Atezolizumab

    Participants will receive Atezolizumab for 16 cycles, or up to 1 year (whichever occurs first)

    Drug: Atezolizumab

  • Experimental
    Placebo

    Participants will receive Placebo for 16 cycles, or up to 1 year (whichever occurs first).

    Drug: Placebo

Interventions

  • DrugAtezolizumab

    Atezolizumab intravenous infusion will be administered at a fixed dose on Day 1 of each 21-day cycle for 16 cycles.

  • DrugPlacebo

    Placebo intravenous infusion will be administered a fixed dose on Day 1 of each 21-day cycle for 16 cycles.

05

What researchers measure

Primary outcomes

  1. Investigator-Assessed Event-Free Survival (INV-assessed EFS)

    EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.

    Time frame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

Secondary outcomes

  1. Overall Survival (OS)

    OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.

    Time frame: Randomization to death from any cause (up to 5 years, 5 months)

  2. Independent Review Facility (IRF) Assessed EFS

    EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.

    Time frame: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

  3. Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years

    EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.

    Time frame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years

  4. Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years

    EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by the investigator, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.

    Time frame: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years

  5. Percentage of Participants Event-Free for OS at 2, 3, and 5 Years

    OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 2, 3 and 5 years.

    Time frame: From randomization to OS event or date last known to be alive at 2, 3, and 5 Years

  6. Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score

    EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptoms (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in PF was assessed using the PF scale, where participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet) was scored on a 4-point scale (1=Not at All to 4=Very Much). Scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.

    Time frame: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)

  7. Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score

    EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding Global Health Status (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized. Scores range from 0-100. A higher score indicates a better outcome.

    Time frame: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)

  8. Number of Participants With at Least One Adverse Event (AE)

    An AE is untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.

    Time frame: From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months)

  9. Serum Concentration of Atezolizumab

    Time frame: Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year)

  10. Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab

    Number of participants positive for Treatment Emergent ADA is the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period.

    Time frame: Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days)

06

Results

Posted Oct 9, 2024

Participant flow

Participants took part in the study across 128 investigative sites in 23 countries from 03 April 2018 to 06 March 2024.

Participant flow — Overall Study
MilestonePlaceboAtezolizumab
Started203203
Received at least one dose of study drug203202
Completed00
Not completed203203
Withdrew: Death6770
Withdrew: Lost to follow-up42
Withdrew: Physician decision01
Withdrew: Study terminated by sponsor120121
Withdrew: Withdrawal by subject129

Outcome measures

PrimaryInvestigator-Assessed Event-Free Survival (INV-assessed EFS)

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.

Time frame:
Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
Reported as:
Median · months
Investigator-Assessed Event-Free Survival (INV-assessed EFS)
monthsPlaceboAtezolizumab
Investigator-Assessed Event-Free Survival (INV-assessed EFS)52.73 (41.43 to NA)59.47 (46.75 to NA)
Statistical analysis
  • Placebo vs Atezolizumab · Log Rank · p = 0.6804 · Hazard ratio (hr): 0.94 · 95% CI 0.70 to 1.26HR was estimated by Cox regression.
SecondaryOverall Survival (OS)

OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.

Time frame:
Randomization to death from any cause (up to 5 years, 5 months)
Reported as:
Median · months
Overall Survival (OS)
monthsPlaceboAtezolizumab
Overall Survival (OS)NA (NA to NA)NA (59.47 to NA)
Statistical analysis
  • Placebo vs Atezolizumab · Log Rank · p = 0.8371 · Hazard ratio (hr): 0.96 · 95% CI 0.68 to 1.36HR was estimated by Cox regression.
SecondaryIndependent Review Facility (IRF) Assessed EFS

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.

Time frame:
Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)
Reported as:
Median · months
Independent Review Facility (IRF) Assessed EFS
monthsPlaceboAtezolizumab
Independent Review Facility (IRF) Assessed EFS52.73 (43.10 to NA)59.47 (45.17 to NA)
Statistical analysis
  • Placebo vs Atezolizumab · Log Rank · p = 0.9115 · Hazard ratio (hr): 0.98 · 95% CI 0.73 to 1.32HR was estimated by Cox regression
SecondaryPercentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.

Time frame:
From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years
Reported as:
Number · percentage of participants
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years
percentage of participantsPlaceboAtezolizumab
1 Year72.59 (66.41 to 78.77)71.92 (65.68 to 78.16)
2 Year65.85 (59.25 to 72.46)66.31 (59.73 to 72.89)
3 Year59.87 (52.99 to 66.76)61.07 (54.25 to 67.88)
4 Year54.71 (47.51 to 61.90)54.72 (47.52 to 61.91)
Statistical analysis
  • Placebo vs Atezolizumab · Z test · p = 0.8816 · Difference in event free rate: -0.67 · 95% CI -9.45 to 8.11
  • Placebo vs Atezolizumab · Z test · p = 0.9234 · Difference in event free rate: 0.46 · 95% CI -8.86 to 9.78
  • Placebo vs Atezolizumab · Z test · p = 0.8090 · Difference in event free rate: 1.19 · 95% CI -8.49 to 10.88
  • Placebo vs Atezolizumab · Z test · p = 0.9985 · Difference in event free rate: 0.01 · 95% CI -10.17 to 10.19
SecondaryPercentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by the investigator, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.

Time frame:
From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years
Reported as:
Number · percentage of participants
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years
percentage of participantsPlaceboAtezolizumab
1 Year70.84 (64.58 to 77.10)76.01 (70.09 to 81.93)
2 Year63.81 (57.17 to 70.45)67.41 (60.90 to 73.92)
3 Year58.57 (51.73 to 65.41)61.71 (54.94 to 68.49)
4 Year55.51 (48.49 to 62.52)56.82 (49.75 to 63.88)
Statistical analysis
  • Placebo vs Atezolizumab · Z test · p = 0.2393 · Difference in event free rate: 5.17 · 95% CI -3.44 to 13.79
  • Placebo vs Atezolizumab · Z test · p = 0.4472 · Difference in event free rate: 3.61 · 95% CI -5.69 to 12.90
  • Placebo vs Atezolizumab · Z test · p = 0.5222 · Difference in event free rate: 3.14 · 95% CI -6.49 to 12.77
  • Placebo vs Atezolizumab · Z test · p = 0.7967 · Difference in event free rate: 1.31 · 95% CI -8.64 to 11.26
SecondaryPercentage of Participants Event-Free for OS at 2, 3, and 5 Years

OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 2, 3 and 5 years.

Time frame:
From randomization to OS event or date last known to be alive at 2, 3, and 5 Years
Reported as:
Number · percentage of participants
Percentage of Participants Event-Free for OS at 2, 3, and 5 Years
percentage of participantsPlaceboAtezolizumab
2 Year79.23 (73.64 to 84.82)82.00 (76.68 to 87.33)
3 Year73.59 (67.48 to 79.70)72.34 (66.11 to 78.56)
5 Year62.00 (53.46 to 70.55)60.93 (48.01 to 73.86)
Statistical analysis
  • Placebo vs Atezolizumab · Z test · p = 0.4819 · Difference in event free rate: 2.77 · 95% CI -4.95 to 10.49
  • Placebo vs Atezolizumab · Z test · p = 0.7783 · Difference in event free rate: -1.25 · 95% CI -9.97 to 7.47
  • Placebo vs Atezolizumab · Z test · p = 0.8924 · Difference in event free rate: -1.07 · 95% CI -16.56 to 14.42
SecondaryChange From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score

EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptoms (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in PF was assessed using the PF scale, where participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet) was scored on a 4-point scale (1=Not at All to 4=Very Much). Scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.

Time frame:
Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)
Reported as:
Mean · score on a scale
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score
score on a scalePlaceboAtezolizumab
Baseline (Cycle 1 Day 1)82.78 ± 16.3683.46 ± 16.79
Change at Cycle 2 Day 12.40 ± 11.09-0.58 ± 10.54
Change at Cycle 3 Day 13.75 ± 12.03-0.13 ± 12.62
Change at Cycle 4 Day 12.90 ± 13.000.77 ± 13.42
Change at Cycle 5 Day 14.69 ± 13.861.60 ± 12.15
Change at Cycle 6 Day 14.03 ± 12.762.18 ± 13.87
Change at Cycle 7 Day 14.33 ± 13.073.56 ± 13.68
Change at Cycle 8 Day 14.63 ± 13.073.19 ± 13.71
Change at Cycle 9 Day 14.62 ± 13.862.96 ± 14.41
Change at Cycle 10 Day 14.41 ± 14.302.12 ± 14.22
Change at Cycle 11 Day 13.82 ± 14.203.69 ± 12.43
Change at Cycle 12 Day 14.35 ± 15.233.05 ± 14.89
Change at Cycle 13 Day 15.62 ± 13.633.30 ± 15.02
Change at Cycle 14 Day 16.73 ± 13.673.20 ± 13.36
Change at Cycle 15 Day 16.13 ± 13.113.99 ± 12.92
Change at Cycle 16 Day 15.92 ± 14.854.11 ± 12.88
Change at Study Discontinuation2.94 ± 16.522.70 ± 14.20
Change at Follow Up 11.47 ± 16.36-6.63 ± 24.41
Change at Follow Up 2-1.15 ± 18.100.19 ± 17.34
Change at Follow Up 3-0.81 ± 17.172.68 ± 18.75
Change at Follow Up 4-1.90 ± 18.62-2.56 ± 28.57
Change at Follow Up 5-2.00 ± 26.21-6.03 ± 35.58
Change at Follow Up 6-3.61 ± 18.08-3.24 ± 23.84
Change at Follow Up 7-6.75 ± 21.851.54 ± 24.82
Change at Follow Up 8-13.08 ± 28.961.36 ± 33.11
Change at Follow Up 92.88 ± 14.384.63 ± 17.36
Change at Follow Up 10-16.43 ± 32.503.33 ± 13.80
Change at Follow Up 11-10.00 ± 35.31-16.67 ± 24.65
Change at Follow Up 12-6.67 ± 8.430.00 ± 14.40
Change at Follow Up 13-5.71 ± 7.134.44 ± 10.18
Change at Follow Up 14-17.78 ± 42.86-6.67 ± 0
Change at Follow Up 15-5.00 ± 6.38—
Change at Follow Up 162.22 ± 10.18—
Change at Follow Up 17-3.33 ± 4.71—
Change at Follow Up 1813.33 ± 0—
SecondaryChange From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score

EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding Global Health Status (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized. Scores range from 0-100. A higher score indicates a better outcome.

Time frame:
Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)
Reported as:
Mean · score on a scale
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score
score on a scalePlaceboAtezolizumab
Baseline (Cycle 1 Day 1)66.92 ± 21.4167.54 ± 20.79
Change at Cycle 2 Day 12.99 ± 20.320.09 ± 18.33
Change at Cycle 3 Day 14.87 ± 24.020.49 ± 17.35
Change at Cycle 4 Day 16.05 ± 21.041.34 ± 17.33
Change at Cycle 5 Day 15.29 ± 22.801.19 ± 18.25
Change at Cycle 6 Day 14.66 ± 23.813.17 ± 18.01
Change at Cycle 7 Day 17.25 ± 21.714.09 ± 17.47
Change at Cycle 8 Day 17.58 ± 21.484.25 ± 19.93
Change at Cycle 9 Day 16.30 ± 23.203.00 ± 17.93
Change at Cycle 10 Day 17.83 ± 22.293.85 ± 17.12
Change at Cycle 11 Day 17.65 ± 21.212.64 ± 17.35
Change at Cycle 12 Day 17.47 ± 22.522.60 ± 17.75
Change at Cycle 13 Day 18.45 ± 21.372.94 ± 18.41
Change at Cycle 14 Day 16.91 ± 21.823.39 ± 17.04
Change at Cycle 15 Day 17.21 ± 21.585.27 ± 18.13
Change at Cycle 16 Day 16.30 ± 22.876.05 ± 17.83
Change at Study Discontinuation3.86 ± 23.641.55 ± 18.41
Change at Follow Up 11.50 ± 25.01-5.83 ± 25.32
Change at Follow Up 24.67 ± 21.33-0.95 ± 21.73
Change at Follow Up 3-1.77 ± 18.842.53 ± 18.57
Change at Follow Up 40.74 ± 25.323.87 ± 22.51
Change at Follow Up 53.16 ± 23.194.76 ± 23.36
Change at Follow Up 66.32 ± 23.111.85 ± 17.28
Change at Follow Up 72.45 ± 23.34-10.26 ± 23.11
Change at Follow Up 8-8.33 ± 32.002.27 ± 11.84
Change at Follow Up 93.70 ± 17.24-1.85 ± 12.34
Change at Follow Up 10-15.00 ± 50.149.38 ± 9.38
Change at Follow Up 11-4.63 ± 50.88-4.17 ± 19.84
Change at Follow Up 1220.00 ± 40.23-14.58 ± 20.83
Change at Follow Up 1311.11 ± 38.61-2.78 ± 12.73
Change at Follow Up 148.33 ± 11.79-16.67 ± 0
Change at Follow Up 1514.58 ± 34.94—
Change at Follow Up 162.78 ± 12.73—
Change at Follow Up 17-8.33 ± 11.79—
Change at Follow Up 188.33 ± 11.79—
SecondaryNumber of Participants With at Least One Adverse Event (AE)

An AE is untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.

Time frame:
From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months)
Reported as:
Count of participants · Participants
Number of Participants With at Least One Adverse Event (AE)
ParticipantsPlaceboAtezolizumab
Number of Participants With at Least One Adverse Event (AE)186192
SecondarySerum Concentration of Atezolizumab
Time frame:
Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year)
Reported as:
Geometric mean · micrograms per milliliters (ug/mL)
Serum Concentration of Atezolizumab
micrograms per milliliters (ug/mL)Atezolizumab
Cycle 1 Day 1: PredoseNA ± NA
Cycle 1 Day 1: 0.5 hours Post-dose447 ± 27.1
Cycle 2 Day 1: Predose99.2 ± 31.1
Cycle 4 Day 1: Predose186 ± 64.3
Cycle 8 Day 1: Predose238 ± 40.6
Cycle 16 Day 1: Predose257 ± 40.3
Study Discontinuation178 ± 141.0
SecondaryNumber of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab

Number of participants positive for Treatment Emergent ADA is the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period.

Time frame:
Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days)
Reported as:
Count of participants · Participants
Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab
ParticipantsAtezolizumab
Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab13

Adverse events

Collected over For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo69/203 (34%)32/203 (15.8%)144/203 (70.9%)
Atezolizumab70/202 (34.7%)32/202 (15.8%)155/202 (76.7%)
Most frequent serious events
Showing 10 of 74
Most frequent serious events
EventPlaceboAtezolizumab
PneumoniaInfections and infestations1/2036/202
Gastrointestinal haemorrhageGastrointestinal disorders1/2032/202
DeathGeneral disorders1/2032/202
CellulitisInfections and infestations2/2030/202
Pneumonia aspirationInfections and infestations2/2031/202
Cerebrovascular accidentNervous system disorders2/2031/202
Laryngeal oedemaRespiratory, thoracic and mediastinal disorders2/2031/202
Myocardial infarctionCardiac disorders0/2031/202
Salivary gland fistulaGastrointestinal disorders0/2031/202
Implant site painGeneral disorders0/2031/202
Most frequent other events
Showing 10 of 23
Most frequent other events
EventPlaceboAtezolizumab
HypothyroidismEndocrine disorders34/20354/202
FatigueGeneral disorders26/20329/202
DiarrhoeaGastrointestinal disorders10/20326/202
PruritusSkin and subcutaneous tissue disorders15/20323/202
ArthralgiaMusculoskeletal and connective tissue disorders16/20322/202
LymphopeniaBlood and lymphatic system disorders22/2038/202
AnaemiaBlood and lymphatic system disorders18/20319/202
Dry mouthGastrointestinal disorders16/20318/202
CoughRespiratory, thoracic and mediastinal disorders12/20317/202
RashSkin and subcutaneous tissue disorders17/20313/202

Baseline characteristics

Intent-to-Treat (ITT) population included all randomized participants, regardless of whether they received any of the assigned treatment.

Age, Continuous
Age, Continuous(years)PlaceboAtezolizumabTotal
Mean57.7 ± 10.159.4 ± 8.558.5 ± 9.4
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboAtezolizumabTotal
Female293564
Male174168342
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboAtezolizumabTotal
Hispanic or Latino131124
Not Hispanic or Latino181183364
Unknown or Not Reported9918
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboAtezolizumabTotal
American Indian or Alaska Native011
Asian6168129
Native Hawaiian or Other Pacific Islander000
Black or African American112
White135121256
More than one race000
Unknown or Not Reported61218
Human papilloma virus (HPV) Status
Human papilloma virus (HPV) Status(Participants)PlaceboAtezolizumabTotal
Negative166168334
Positive373572
Type of Definitive Local Therapy
Type of Definitive Local Therapy(Participants)PlaceboAtezolizumabTotal
Primary Surgery7879157
No Primary Surgery125124249
Response to Definitive Local Therapy
Response to Definitive Local Therapy(Participants)PlaceboAtezolizumabTotal
Complete Response (CR)170170340
Partial Response (PR) or Stable Disease (SD)333366
07

Study locations

135 sites
  • City of Hope National Medical Center
    Duarte, California 91010, United States
  • University of California San Diego Medical Center; Moores Cancer Center
    La Jolla, California 92093, United States
  • UCLA Hematology/Oncology
    Santa Monica, California 90404, United States
  • Miami Cancer Institute of Baptist Health, Inc.
    Miami, Florida 33176, United States
  • Woodlands Medical Specialists, P.A.
    Pensacola, Florida 32503, United States
  • Winship Cancer Institute of Emory University
    Atlanta, Georgia 30329, United States
  • Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
    Marietta, Georgia 30060, United States
  • Cancer Center of Kansas
    Wichita, Kansas 67214-3728, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Billings Clinic Research Center
    Billings, Montana 59101, United States
  • Cleveland Clinic; Taussig Cancer Institute
    Cleveland, Ohio 44195, United States
  • Blue Ridge Cancer Care
    Roanoke, Virginia 24014, United States
  • St George Hospital
    Kogarah, New South Wales 2217, Australia
  • Adelaide Cancer Centre
    Kurralta Park, South Australia 5037, Australia
  • Peter MacCallum Cancer Center
    North Melbourne, Victoria 3051, Australia
  • Sir Charles Gairdner Hospital
    Nedlands, Western Australia 6009, Australia
  • Clinique Ste-Elisabeth
    Namur, 5000, Belgium
  • Santa Casa de Misericordia de Salvador
    Salvador, BA 40050-410, Brazil
  • Hospital do Cancer de Pernambuco - HCP
    Recife, PE 50040-000, Brazil
  • Instituto Nacional de Cancer - INCa; Oncologia
    Rio de Janeiro, RJ 20560-120, Brazil
  • Hospital Nossa Senhora da Conceicao
    Porto Alegre, RS 90040-373, Brazil
  • Hospital Sao Lucas - PUCRS
    Porto Alegre, RS 90610-000, Brazil
  • Faculdade de Medicina do ABC - FMABC
    Santo Andre, SP 09060-650, Brazil
  • Instituto do Cancer do Estado de Sao Paulo - ICESP
    Sao Paulo, SP 01246-000, Brazil
  • Cross Cancer Institute
    Edmonton, Alberta T6G 1Z2, Canada
  • Cancer Care Manitoba
    Winnipeg, Manitoba R3E 0V9, Canada
  • London Health Sciences Centre
    London, Ontario N6A 4L6, Canada
  • Beijing Cancer Hospital
    Beijing, 100142, China
  • West China Hospital, Sichuan University
    Chengdu, 610041, China
  • Fujian Cancer Hospital
    Fuzhou, 350014, China
  • Fudan University Shanghai Cancer Center
    Shanghai City, 200120, China
  • Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    Shanghai, 200011, China
  • Shanghai East Hospital
    Shanghai, China
  • Tianjin Medical University General Hospital
    Tianjin, 300052, China
  • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    Wuhan City, 430023, China
  • Zhejiang Cancer Hospital
    Zhejiang, 310022, China
  • Institut Sainte Catherine
    Avignon, 84082, France
  • Centre Georges Francois Leclerc
    Dijon, 21000, France
  • CENTRE LEON BERARD; Département d?Hématologie et d?Oncologie
    Lyon, 69373, France
  • Hopital Timone Adultes; Oncologie Medicale Et Usp
    Marseille, 13385, France
  • ICM; Radiotherapie
    Montpellier Cedex 5, 34298, France
  • Hopital Tenon; Oncologie Radiotherapie
    Paris, 75970, France
  • CHU Bordeaux
    Pessac, 33604, France
  • Hôpitaux D'Instruction Des Armees Begin
    St Mande, 94160, France
  • Gustave Roussy Cancer Campus; Radiotherapie
    VILLEJUIF Cedex, 94805, France
  • Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie
    Bonn, 53127, Germany
  • Universitätsklinikum Freiburg, Klinik für Strahlenheilkunde
    Freiburg, 79106, Germany
  • Klinikum d. Uni. München; Campus Großhadern; Klinik und Poliklinik f. Strahlenthera. und Radioonko
    München, 81377, Germany
  • Universitätsmedizin Rostock, Klinik und Poliklinik für Strahlentherapie; Zentrum für Radiologie
    Rostock, 18059, Germany
  • Orszagos Onkologial Intezet; Onkologiai Osztaly X
    Budapest, 1122, Hungary
  • Budapesti Uzsoki Utcai Kórház
    Budapest, 1145, Hungary
  • Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
    Pécs, 7623, Hungary
  • Medanta-The Medicity
    Gurgaon, Haryana 122001, India
  • Tata Memorial Hospital; Dept of Medical Oncology
    Mumbai, Maharashtra 400012, India
  • Istituto Nazionale Tumori Fondazione G. Pascale; S.C. Oncol. Medica Testa-Collo e Sarcoma
    Napoli, Campania 80131, Italy
  • Ospedale Umberto I ASL di Ravenna Presidio Ospedaliero di Lugo
    Lugo, Emilia-Romagna 48022, Italy
  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
    Meldola, Emilia-Romagna 47014, Italy
  • Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
    Roma, Lazio 00161, Italy
  • Ospedale Civile; Servizio Oncologia
    Savona, Liguria 17100, Italy
  • Spedali Civili di Brescia
    Brescia, Lombardia 25123, Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo
    Milano, Lombardia 20133, Italy
  • Asst Santi Paolo E Carlo; Unita Operativa Di Oncologia Medica
    Milano, Lombardia 20142, Italy
  • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
    Rozzano, Lombardia 20089, Italy
  • Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
    Firenze, Toscana 50134, Italy
  • IOV - Istituto Oncologico Veneto IRCCS
    Padova, Veneto 35128, Italy
  • Aichi Cancer Center Hospital
    Aichi, 464-8681, Japan
  • National Cancer Center Hospital East
    Chiba, 277-8577, Japan
  • National Hospital Organization Kyushu Cancer Center
    Fukuoka, 811-1395, Japan
  • Hokkaido University Hospital
    Hokkaido, 060-8648, Japan
  • Kobe University Hospital
    Hyogo, 650-0017, Japan
  • Miyagi Cancer Center
    Miyagi, 981-1293, Japan
  • Okayama University Hospital
    Okayama, 700-8558, Japan
  • Osaka International Cancer Institute
    Osaka, 541-8567, Japan
  • Shizuoka Cancer Center
    Shizuoka, 411-8777, Japan
  • National Cancer Center Hospital
    Tokyo, 104-0045, Japan
  • The Jikei University Hospital
    Tokyo, 105-8471, Japan
  • Tokyo Medical and Dental University Hospital
    Tokyo, 113-8519, Japan
  • The Cancer Institute Hospital of JFCR
    Tokyo, 135-8550, Japan
  • Tokyo Medical University Hospital
    Tokyo, 160-0023, Japan
  • Seoul National University Bundang Hospital
    Seongnam-si, 463-707, Korea, Republic of
  • Seoul National University Hospital
    Seoul, 03080, Korea, Republic of
  • Asan Medical Center
    Seoul, 05505, Korea, Republic of
  • Samsung Medical Center
    Seoul, 06351, Korea, Republic of
  • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
    Gdansk, 80-214, Poland
  • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
    Gliwice, 44-101, Poland
  • Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowotworów G?owy i Szyi
    Warszawa, 02-781, Poland
  • IPO de Coimbra; Servico de Oncologia Medica
    Coimbra, 3000-075, Portugal
  • Hospital de Santa Maria; Servico de Oncologia Medica
    Lisboa, 1649-035, Portugal
  • IPO do Porto; Servico de Oncologia Medica
    Porto, 4200-072, Portugal
  • Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
    Krasnoyarsk, Krasnodar 660133, Russian Federation
  • Moscow City Oncology Hospital #62
    Moscovskaya Oblast, Moskovskaja Oblast 143423, Russian Federation
  • Main Military Clinical Hospital named after N.N. Burdenko
    Moscow, Moskovskaja Oblast 105229, Russian Federation
  • P.A. Herzen Oncological Inst. ; Oncology
    Moscow, Moskovskaja Oblast 125248, Russian Federation
  • First MSMU n.a. Sechenov Univercity Hospital 1; Plastic surgery
    Moskva, Moskovskaja Oblast 119435, Russian Federation
  • FSAI Treatment and rehabilitation Centre Ministry of Health; Clinical research and chemotherapy.
    Moskva, Moskovskaja Oblast 125367, Russian Federation
  • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
    Saint-Petersburg, Sankt Petersburg 197758, Russian Federation
  • Sverdlovsk Regional Oncology Dispensary; Chemotherapy
    Ekaterinburg, Sverdlovsk 620905, Russian Federation
  • Novosibirsk Regional Oncological Dispancer
    Novosibirsk, 630108, Russian Federation
  • BHI of Omsk region Clinical Oncology Dispensary
    Omsk, 644013, Russian Federation
  • Tomsk scientific research institute of oncology SO RAMN, PAD; Pathological
    Tomsk, 634028, Russian Federation

Showing the first 100 of 135 sites across 23 countries.

08

References and documents

Study documents

  • Study protocol · Feb 24, 2023
  • Statistical analysis plan · Mar 30, 2022

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03452137
Lead sponsor
Hoffmann-La Roche
Responsible party
Sponsor
First posted
Mar 2, 2018
Start date
Apr 3, 2018
Primary completion
Sep 27, 2023
Completion
Mar 6, 2024
Results posted
Oct 9, 2024
Last update
Oct 9, 2024

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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