Clinical Trial Results:
A Phase IIIb, Single Arm Study of Carboplatin or Cisplatin Plus Etoposide with Atezolizumab (Anti-PD-L1 Antibody) in Patients with Untreated Extensive-Stage Small Cell Lung Cancer
Summary
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EudraCT number |
2019-002784-10 |
Trial protocol |
ES |
Global end of trial date |
14 Dec 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Dec 2023
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First version publication date |
14 Dec 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ML41599
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Roche Farma S.A. (Soc. Unipersonal)
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Sponsor organisation address |
C/Ribera del Lora 50, Madrid, Spain, 28042
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Public contact |
Roche Farma S.A. (Soc. Unipersonal), Roche Farma S.A. (Soc. Unipersonal), 34 913253700, spain.start_up_unit@roche.com
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Scientific contact |
Roche Farma S.A. (Soc. Unipersonal), Roche Farma S.A. (Soc. Unipersonal), 34 913253700, spain.start_up_unit@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Dec 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Dec 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This study is being conducted to evaluate the safety of atezolizumab + carboplatin or cisplatin + etoposide as first-line treatment for extensive-stage small cell lung cancer.
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Protection of trial subjects |
All study subjects were required to read and sign and Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Dec 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 155
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Worldwide total number of subjects |
155
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EEA total number of subjects |
155
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
73
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From 65 to 84 years |
81
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85 years and over |
1
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Recruitment
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Recruitment details |
The study was conducted at 29 centers in one country. | ||||||||||||||||
Pre-assignment
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Screening details |
A total of 155 participants were enrolled at 29 centers. | ||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
Arms
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Arm title
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Atezolizumab + Cisplatin/Carboplatin + Etoposide | ||||||||||||||||
Arm description |
Participants will receive the following treatment regimen: atezolizumab + cisplatin/carboplatin + etoposide. Induction treatment will be administered on a 21-day cycle for four or six cycles (according to investigator's choice). Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first). | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Atezolizumab
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Investigational medicinal product code |
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Other name |
Tecentriq
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Atezolizumab will be administered by intravenous infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
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Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) of 5 mg/mL/min on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).
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Investigational medicinal product name |
Etoposide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Etoposide will be administered intravenously at a dose of 100 mg/m^2 on Days 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4).
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Investigational medicinal product name |
Cisplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (75 mg/m^2) after completion of atezolizumab on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).
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Baseline characteristics reporting groups
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Reporting group title |
Atezolizumab + Cisplatin/Carboplatin + Etoposide
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Reporting group description |
Participants will receive the following treatment regimen: atezolizumab + cisplatin/carboplatin + etoposide. Induction treatment will be administered on a 21-day cycle for four or six cycles (according to investigator's choice). Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Atezolizumab + Cisplatin/Carboplatin + Etoposide
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Reporting group description |
Participants will receive the following treatment regimen: atezolizumab + cisplatin/carboplatin + etoposide. Induction treatment will be administered on a 21-day cycle for four or six cycles (according to investigator's choice). Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first). |
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End point title |
Mean Treatment Duration of Atezolizumab [1] | ||||||||
End point description |
Treatment duration is defined as the total number of days from first treatment administration to the last treatment administration +1.
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End point type |
Primary
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End point timeframe |
Baseline up to approximately 36 months
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Number of Cycles of Carboplatin or Cisplatin [2] | ||||||||
End point description |
There is 4 or 6 cycles of carboplatin or cisplatin. Each cycle is 21 days. A participant can have cycles of carboplatin and cisplatin during induction phase.
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End point type |
Primary
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End point timeframe |
From Baseline up to 18 months
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Number of Cycles of Atezolizumab (Both Induction and Maintenance Phases) [3] | ||||||||
End point description |
The induction phase of the study will consist of four or six cycles of atezolizumab plus chemotherapy, with each cycle being 21 days in duration. After the induction phase, patients will begin maintenance therapy with atezolizumab every 3 weeks.
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End point type |
Primary
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End point timeframe |
Baseline up to 36 months
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Number of Cycles of Etoposide [4] | ||||||||
End point description |
There is 4 or 6 cycles of etoposide. Each cycle is 21 days.
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End point type |
Primary
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End point timeframe |
From baseline up to 18 months
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Dose Interruption [5] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Transient or Permanent Dose Interruption [6] | ||||||||||||
End point description |
A participant can be counted in several categories.
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End point type |
Primary
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End point timeframe |
From baseline to 36 months
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Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Receiving Cycles of Chemotherapy [7] | ||||||||||||||||
End point description |
The cycles range from less than 4 cycles to 6 cycles. Each cycle is 21 days.
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End point type |
Primary
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End point timeframe |
From Baseline to 18 months
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Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Treatment Emergent AEs Leading to Study Drug Discontinuation or Interruption by Primary System Organ Class [8] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Treatment-emergent AE (TEAE) is defined as an AE that began after the start of trial medication treatment. The dictionary used was MedDRA v25.1
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Taking Concomitant Medications (Corticosteroids) by Anatomic Class [9] | ||||||||||||||||||||
End point description |
Concomitant therapy includes any medication used by a patient from 7 days prior to screening until the treatment discontinuation visit. Participants with premedication are included in the table. A medication can be counted in several categories.
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Taking Concomitant Medications by Anatomic Class [10] | ||||||||||||||||||||||||||||||||||||
End point description |
Concomitant therapy includes any medication used by a patient from 7 days prior to screening until the treatment discontinuation visit. Participants with premedication are included in the table. A medication can be counted in several categories.
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Kaplan-Meier Cumulative Incidence Probability of Treatment Emergent AEs of Special Interest During Treatment Period [11] | ||||||||||||||||||
End point description |
Out of 155 participants, 148 participants were censored and there were 7 events. Event is any patient who has experienced at least one treatment emergent AE of special interest during treatment period. Censor is any patient who has not experienced a treatment emergent AE of special interest during treatment period.
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End point type |
Primary
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End point timeframe |
From baseline to 36 months
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Treatment Emergent AEs [12] | ||||||||||||||||
End point description |
Percentage of participants with at least one treatment AE. Clopper-Pearson is used for 95% confidence interval.
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Treatment Related AEs [13] | ||||||||||||||||
End point description |
Percentage of participants with at least one treatment emergent AE. Clopper-Pearson is used for 95% confidence interval.
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Treatment Related SAEs [14] | ||||||||||||||||
End point description |
Percentage of participants with at least one treatment emergent AE. Clopper-Pearson is used for 95% confidence interval.
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End point type |
Primary
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End point timeframe |
From baseline up to 36 months
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Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Treatment Emergent AEs of Special Interest [15] | ||||||||||||||||
End point description |
Percentage of participants with at least one treatment emergent AE of special interest. Clopper-Pearson is used for 95% confidence interval.
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End point type |
Primary
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End point timeframe |
from baseline up to 36 months
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Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Change in Diastolic Blood Pressure [16] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
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End point type |
Primary
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End point timeframe |
Baseline, Induction Phase(IP) Cycle(C) 1 pre- & post-dose, IPC2 pre- & post-dose, IPC3 pre- & post-dose, IPC4 pre- & post-dose, Maintenance Phase(MP) Visit(V) 1 pre- & post-dose, MPV2 pre- & post-dose, MPV3 pre- & post-dose, MPV4 pre- & post-dose
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Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Change in Systolic Blood Pressure [17] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
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End point type |
Primary
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End point timeframe |
Baseline, IPC1 pre- & post-dose, IPC2 pre- & post-dose, IPC3 pre- & post-dose, IPC4 pre- & post-dose, MPV1 pre- & post-dose, MPV2 pre- & post-dose, MPV3 pre- & post-dose, MPV4 pre- & post-dose
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Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Change in Weight [18] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
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End point type |
Primary
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End point timeframe |
Baseline, IPC1 pre- & post-dose, IPC2 pre- & post-dose, IPC3 pre- & post-dose, IPC4 pre- & post-dose, MPV1 pre- & post-dose, MPV2 pre- & post-dose, MPV3 pre- & post-dose, MPV4 pre- & post-dose
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Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Change in Pulse Rate [19] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
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End point type |
Primary
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End point timeframe |
Baseline, IPC1 pre- & post-dose, IPC2 pre- & post-dose, IPC3 pre- & post-dose, IPC4 pre- & post-dose, MPV1 pre- & post-dose, MPV2 pre- & post-dose, MPV3 pre- & post-dose, MPV4 pre- & post-dose
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Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
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No statistical analyses for this end point |
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End point title |
Mean Change in Respiratory Rate [20] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
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End point type |
Primary
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End point timeframe |
Baseline, IPC1 pre- & post-dose, IPC2 pre- & post-dose, IPC3 pre- & post-dose, IPC4 pre- & post-dose, MPV1 pre- & post-dose, MPV2 pre- & post-dose, MPV3 pre- & post-dose, MPV4 pre- & post-dose
|
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Notes [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean Change in Lymphocytes [21] | ||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, IP Cycle 2, IP Cycle 3, IP Cycle 4, MP Visit 1, MP Visit 2, MP Visit 3, MP Visit 4
|
||||||||||||||||||||||||
Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean Change in Neutrophils [22] | ||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, IP Cycle 2, IP Cycle 3, IP Cycle 4, MP Visit 1, MP Visit 2, MP Visit 3, MP Visit 4
|
||||||||||||||||||||||||
Notes [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean Change in Platelets [23] | ||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, IP Cycle 2, IP Cycle 3, IP Cycle 4, MP Visit 1, MP Visit 2, MP Visit 3, MP Visit 4
|
||||||||||||||||||||||||
Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean Change in Neutrophil-to-Lymphocyte Ratio [24] | ||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, IP Cycle 2, IP Cycle 3, IP Cycle 4, MP Visit 1, MP Visit 2, MP Visit 3, MP Visit 4
|
||||||||||||||||||||||||
Notes [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean Change in Platelet-to-Lymphocyte Ratio [25] | ||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, IP Cycle 2, IP Cycle 3, IP Cycle 4, MP Visit 1, MP Visit 2, MP Visit 3, MP Visit 4
|
||||||||||||||||||||||||
Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean Change to Lactate Dehydrogenase [26] | ||||||||||||||||||||||||
End point description |
The mean changes are recorded at baseline, during and following study treatment administration.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, IP Cycle 2, IP Cycle 3, IP Cycle 4, MP Visit 1, MP Visit 2, MP Visit 3, MP Visit 4
|
||||||||||||||||||||||||
Notes [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There was no statistical analysis done for the outcome measure. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Progression Free Survival (PFS) | ||||||||
End point description |
PFS, defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to approximately 36 months)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Overall Survival (OS) | ||||||||
End point description |
OS, defined as the time from initiation of study treatment to death from any cause.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline until death (up to approximately 36 months)
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Objective Response Rate (ORR) | ||||||||||||
End point description |
ORR, defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to approximately 36 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Disease Control Rate (DCR) | ||||||||||||
End point description |
DCR, defined as PR, CR and stable disease (SD) as determined by the investigator according to RECIST v1.1.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to approximately 36 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Duration of Response (DOR) | ||||||||
End point description |
DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline to disease progression or death from any cause (whichever occurs first) up to approximately 36 months
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
PFS Rate at 6 Months and 1 Year | ||||||||||||
End point description |
PFS rate at 6 months and 1 year, defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months and 1 year separately, as determined by the investigator according to RECIST v1.1.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to 1 year
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
OS Rate at 6 months, 12 months, 18 months and 24 months | ||||||||||||||||
End point description |
OS rate at 6 months, 12 months, 18 months and 24 months, defined as the proportion of patients who have not experienced death from any cause at 6 months, 12 months, 18 months and 24 months.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline to 24 months or death, whichever occurs first
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Time to Treatment Discontinuation (TTD) | ||||||||
End point description |
TTD, defined as the time from inclusion to
treatment discontinuation for any reason.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to approximately 36 months
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
From baseline up to 24 months
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v25.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atezolizumab + Cisplatin/Carboplatin + Etoposide
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants will receive the following treatment regimen: atezolizumab + cisplatin/carboplatin + etoposide. Induction treatment will be administered on a 21-day cycle for four or six cycles (according to investigator's choice). Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Jul 2020 |
- The new Nanostring GeoMx® Digital Space Profiler (DSP) technology will be applied to the tissue samples submitted at baseline
- The information about FoundationOneLiquid® was updated to reflect the current test specifications.
- Exclusion Criteria section was clarified on patients who are positive for human immunodeficiency virus and who are allowed in the study.
- ‘Permitted Therapy’ section added consolidation radiotherapy.
- ‘Tumor and Response Evaluation’ section was clarified in case a PET-CT scan with no contrast was performed within permitted Screening window, it could be used as baseline test and was clarified that after completion of induction phase tumor assessment, tumor assessments will be required every 9 weeks thereafter.
- In ‘Laboratory Assessments and Biomarker Samples’, for pregnancy test, added local practice is to do it in serum at every cycle.
-In ‘Screening and Baseline Assessments’ section, information on validity of tumor assessments has been amended.
- In ‘Assessments during Treatment’ section, information on validity of tests was amended.
- Option to switch from cisplatin to carboplatin due to inacceptable toxicity was included in chemotherapy management sections.
- Text of sections ‘Subgroup Analyses’, ‘Biomarker Analyses’ and Interim Analyses was updated to reflect statistical plan as per current Protocol.
- CTCAE version was updated from v.4 to v.5.
- The 30-day timeframe to report special situations and non serious AEs associated with special situations is specified. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |