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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03735121




Registration number
NCT03735121
Ethics application status
Date submitted
7/11/2018
Date registered
8/11/2018
Date last updated
25/03/2025

Titles & IDs
Public title
A Study to Investigate Atezolizumab Subcutaneous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Scientific title
A Randomized, Multicenter, Phase Ib/III Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous Compared With Atezolizumab Intravenous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
2018-002328-18
Secondary ID [2] 0 0
BP40657
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - rHuPH20

Experimental: Atezolizumab (Part 2) - Atezolizumab

Experimental: Cohort 1: Atezolizumab+rHuPH20 (Part 1) - Atezolizumab+recombinant human hyaluronidase (rHuPH20), followed by Atezolizumab

Experimental: Cohort 2: Atezolizumab+rHuPH20 (Part 1) - Atezolizumab+rHuPH20, followed by Atezolizumab

Experimental: Cohort 3: Atezolizumab+rHuPH20(Part 1) - Atezolizumab+rHuPH20, followed by Atezolizumab

Experimental: Atezolizumab + rHuPH20 (Part 2) - Atezolizumab + rHuPH20


Treatment: Drugs: Atezolizumab
Atezolizumab will be administered as per the schedule specified in arm or cohort.

Treatment: Drugs: rHuPH20
rHuPH20 will be administered as per the scheduled specified in the cohort for Part 1.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1
Assessment method [1] 0 0
Timepoint [1] 0 0
Pre-dose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
Primary outcome [2] 0 0
Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1
Assessment method [2] 0 0
Timepoint [2] 0 0
Predose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
Primary outcome [3] 0 0
Part 2: Area Under the Concentration-Time Curve From Time Zero to 21 Days (AUC 0-21 d) at Cycle 1
Assessment method [3] 0 0
Timepoint [3] 0 0
From start of dosing up to Day 21 in Cycle 1 (Cycle length= 21 days)
Secondary outcome [1] 0 0
Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Assessment method [1] 0 0
Timepoint [1] 0 0
Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)
Secondary outcome [2] 0 0
Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab
Assessment method [2] 0 0
Timepoint [2] 0 0
Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)
Secondary outcome [3] 0 0
Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab
Assessment method [3] 0 0
Timepoint [3] 0 0
Predose and up to 21 days post dose in Cycle 1 for cohorts 1 and 3 and from predose up to 14 days post last dose in Cycle 1 for cohort 2 (Cycle length= 21 days for cohorts 1 and 3 and 14 days for cohort 2)
Secondary outcome [4] 0 0
Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration
Assessment method [4] 0 0
Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2. Day=D; Cycle=C.
Timepoint [4] 0 0
Cohort 1: Pre&postdose:D1 &postdose: D3,8 of C1; Cohort 2: Pre&postdose: D1 of C1,3 & postdose: D3,8 of C1, Predose: D1 of C2; Cohort 3: Pre& postdose: D1 of C1,2 & postdose: D3,8 of C1, D2,4& 9 of C2& pre dose:D1 of C3
Secondary outcome [5] 0 0
Part 1: Percentage of Participants With Adverse Events (AEs)
Assessment method [5] 0 0
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE 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. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0).
Timepoint [5] 0 0
Baseline up to data cutoff date for primary analysis, April 26, 2022 (up to approximately 17 months)
Secondary outcome [6] 0 0
Part 2: Percentage of Participants With AEs
Assessment method [6] 0 0
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE 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. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0).
Timepoint [6] 0 0
From signing of informed consent form (ICF) until 30 days after last dose of study drug administration in Part 2 (Up to approximately 72 months)
Secondary outcome [7] 0 0
Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1
Assessment method [7] 0 0
Timepoint [7] 0 0
Cycle 1 (Cycle length=21 days)
Secondary outcome [8] 0 0
Part 2: Model Predicted Ctrough at Steady State (Cthrough,ss) of Atezolizumab
Assessment method [8] 0 0
1 cycle=21 days Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo.
Timepoint [8] 0 0
Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)
Secondary outcome [9] 0 0
Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab
Assessment method [9] 0 0
1 cycle=21 days Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo
Timepoint [9] 0 0
Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)
Secondary outcome [10] 0 0
Part 2: Objective Response Rate (ORR)
Assessment method [10] 0 0
ORR is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR.
Timepoint [10] 0 0
From treatment initiation until disease progression or loss of clinical benefit (Up to approximately 72 months).
Secondary outcome [11] 0 0
Part 2: Progression-Free Survival (PFS)
Assessment method [11] 0 0
PFS is defined as the time from study start to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or or death from any cause (whichever occurs first).
Timepoint [11] 0 0
From study start to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 72 months).
Secondary outcome [12] 0 0
Part 2: Overall Survival (OS)
Assessment method [12] 0 0
OS defined as the time from study entry to death from any cause.
Timepoint [12] 0 0
From study start to death from any cause (Up to approximately 72 months)
Secondary outcome [13] 0 0
Part 2: Duration of Response (DOR)
Assessment method [13] 0 0
DOR is defined as the time from first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. Objective response is defined as the percentage of participants having a CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters in the absence of CR.
Timepoint [13] 0 0
From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 72 months)
Secondary outcome [14] 0 0
Part 2: Functioning and Global Health Status Over Time, as Assessed by European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)57
Assessment method [14] 0 0
EORTC IL57 questionnaire has10 items and covers 3 scales: physical functioning (PF), role functioning (RF) \& global health status/quality of life (GHS/QoL) \& 1 item from EORTC Item Library. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks \& short walks; need to stay in bed or a chair; need help with eating, dressing, bathing/using toilet. RF scale has 2 items evaluating extent to which participants are limited in doing work \& pursuing leisure activities in previous week. GHS/QoL scale has 2 items evaluating participants' overall health \& QoL in previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical and role functioning \& a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For each scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 =best possible score. Higher score = better outcome.
Timepoint [14] 0 0
From Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
Secondary outcome [15] 0 0
Part 2: Overall Satisfaction With Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ)
Assessment method [15] 0 0
Modified SWT scale of the CTSQ consist of seven items that measures seven domains related to satisfaction with cancer therapy. These include worthwhile, difficulty, benefits, feelings about side effects, form of therapy, overall satisfaction, and if participants would choose the therapy taking everything into consideration. Each domain is rated on a 5-point scale, with 1 representing the worst response and 5 representing the best response, except in the case of one reverse-scored item. mean of the items are linearly transformed to obtain scores from 0-100, where 100 =best possible score Higher scores are associated with higher satisfaction.
Timepoint [15] 0 0
Day 1 Cycle 3 or at treatment discontinuation visit (Up to approximately 72 months)
Secondary outcome [16] 0 0
Part 2: Overall Patient-reported AE's Burden Over Time, Assessed by the Treatment-related Symptom Burden Item From the EORTC IL57
Assessment method [16] 0 0
The overall patient-reported AE burden was assessed using the a single item from the EORTC IL57 questionnaire i.e To what extent have you been troubled with side-effects from your treatment?. The questions is answered on a 4-point Likert scale where 1="Not at all" to 4="Very much". Higher scores indicates greater AE burden.
Timepoint [16] 0 0
Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
Secondary outcome [17] 0 0
Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration
Assessment method [17] 0 0
Timepoint [17] 0 0
From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months).
Secondary outcome [18] 0 0
Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration Relative to the Prevalence of ADAs at Baseline
Assessment method [18] 0 0
Timepoint [18] 0 0
From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months)
Secondary outcome [19] 0 0
Part 2: Convenience, Potential Time Savings, and Overall Satisfaction With Atezolizumab SC Compared With Atezolizumab IV as Assessed by the Health Care Professional (HCP) SC Versus IV Perspective Questionnaire
Assessment method [19] 0 0
The HCP Subcutaneous Versus IV Perspective Questionnaire consists of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction.
Timepoint [19] 0 0
After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 72 months)
Secondary outcome [20] 0 0
Part 2: Convenience, Ease of Administration, and Overall Satisfaction With Atezolizumab SC Assessed Using HCP Subcutaneous Perspective Questionnaire
Assessment method [20] 0 0
The HCP Subcutaneous Perspective Questionnaire consists of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction.
Timepoint [20] 0 0
After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 72 months)

Eligibility
Key inclusion criteria
* Histologically or cytologically documented locally advanced or metastatic NSCLC
* Prior platinum-containing regimen or disease recurrence = 6 months since prior platinum-based adjuvant/neoadjuvant regimen.
* Measurable disease as defined by RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy =12 weeks
* Adequate hematologic and end-organ function

Additional Inclusion Criteria (Part 2 Only) • Availability of tissue and known epidermal growth factor receptor (EGFR) status
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Uncontrolled or symptomatic hypercalcemia
* Pregnancy or breastfeeding
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
* Severe infection = 4 weeks
* Treatment with therapeutic oral or IV antibiotics = 2 weeks prior to study treatment
* Significant cardiovascular disease
* Prior allogeneic stem cell or solid organ transplantation
* Treatment with a live, attenuated vaccine = 4 weeks
* Treatment with systemic immunostimulatory agents = 4 weeks or 5 half-lives of the drug
* Treatment with systemic immunosuppressive medication = 2 weeks

Additional Exclusion Criteria (Part 2 Only)

• Tested tumor programmed death-ligand-1 (PD-L1) expression status with an intention to treat the patient if positive

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/11/2024
Sample size
Target
Accrual to date
Final
438
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
La Rioja
Country [3] 0 0
Argentina
State/province [3] 0 0
Salta
Country [4] 0 0
Brazil
State/province [4] 0 0
Rio Grande Do Sul
Country [5] 0 0
Brazil
State/province [5] 0 0
Rio de Janeiro
Country [6] 0 0
Chile
State/province [6] 0 0
Recoleta
Country [7] 0 0
Chile
State/province [7] 0 0
Temuco
Country [8] 0 0
Chile
State/province [8] 0 0
Vina Del Mar
Country [9] 0 0
China
State/province [9] 0 0
Changchun
Country [10] 0 0
China
State/province [10] 0 0
Chengdu City
Country [11] 0 0
China
State/province [11] 0 0
Hangzhou City
Country [12] 0 0
China
State/province [12] 0 0
Jinan City
Country [13] 0 0
China
State/province [13] 0 0
Zhengzhou
Country [14] 0 0
Costa Rica
State/province [14] 0 0
San Jose
Country [15] 0 0
France
State/province [15] 0 0
Marseille
Country [16] 0 0
France
State/province [16] 0 0
Saint Herblain
Country [17] 0 0
Greece
State/province [17] 0 0
Asvestochori
Country [18] 0 0
Greece
State/province [18] 0 0
Athens
Country [19] 0 0
Guatemala
State/province [19] 0 0
Ciudad de Guatemala
Country [20] 0 0
Guatemala
State/province [20] 0 0
Guatemala City
Country [21] 0 0
Guatemala
State/province [21] 0 0
Guatemala
Country [22] 0 0
Hungary
State/province [22] 0 0
Matrahaza
Country [23] 0 0
Hungary
State/province [23] 0 0
Törökbálint
Country [24] 0 0
Italy
State/province [24] 0 0
Lombardia
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Latvia
State/province [26] 0 0
Riga
Country [27] 0 0
Mexico
State/province [27] 0 0
Queretaro
Country [28] 0 0
New Zealand
State/province [28] 0 0
Auckland
Country [29] 0 0
New Zealand
State/province [29] 0 0
Christchurch
Country [30] 0 0
New Zealand
State/province [30] 0 0
Hamilton
Country [31] 0 0
New Zealand
State/province [31] 0 0
Tauranga
Country [32] 0 0
Peru
State/province [32] 0 0
Arequipa
Country [33] 0 0
Peru
State/province [33] 0 0
Lima
Country [34] 0 0
Poland
State/province [34] 0 0
Grudzi?dz
Country [35] 0 0
Poland
State/province [35] 0 0
Lodz
Country [36] 0 0
Poland
State/province [36] 0 0
Otwock
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Mordovija
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Moskovskaja Oblast
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Niznij Novgorod
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Murmansk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Samara
Country [43] 0 0
South Africa
State/province [43] 0 0
Cape Town
Country [44] 0 0
South Africa
State/province [44] 0 0
Pretoria
Country [45] 0 0
South Africa
State/province [45] 0 0
Sandton
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Thailand
State/province [48] 0 0
Bangkok
Country [49] 0 0
Thailand
State/province [49] 0 0
Chanthaburi
Country [50] 0 0
Thailand
State/province [50] 0 0
ChiangMai
Country [51] 0 0
Thailand
State/province [51] 0 0
Hat Yai
Country [52] 0 0
Thailand
State/province [52] 0 0
Muang,Udonthani
Country [53] 0 0
Turkey
State/province [53] 0 0
Ankara
Country [54] 0 0
Turkey
State/province [54] 0 0
Istanbul
Country [55] 0 0
Turkey
State/province [55] 0 0
Izmir
Country [56] 0 0
Ukraine
State/province [56] 0 0
Katerynoslav Governorate
Country [57] 0 0
Ukraine
State/province [57] 0 0
Sumy
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03735121