Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer (NSCLC) - Lung Cancer Mutation Consortium (LCMC3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02927301
Recruitment Status : Active, not recruiting
First Posted : October 7, 2016
Results First Posted : May 17, 2021
Last Update Posted : May 17, 2021
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Intervention Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Enrollment 181
Recruitment Details  
Pre-assignment Details

The study was conducted in two parts, a Neoadjuvant Atezolizumab Therapy Phase and an Adjuvant Atezolizumab Therapy Phase. Neoadjuvant therapy consisted of two 21-day cycles with atezolizumab. Following surgery, adjuvant therapy consisted of up to 12 months of atezolizumab in participants who demonstrate clinical benefit with adjuvant therapy. Participant Flow data are for the Neoadjuvant Atezo Therapy Phase.

Adjuvant Atezo Therapy Phase data are not final as study is ongoing.
Arm/Group Title Atezolizumab
Hide Arm/Group Description Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of adjuvant atezolizumab.
Period Title: Overall Study
Started 181
Completed 171
Not Completed 10
Reason Not Completed
Adverse Event             7
Withdrawal by Subject             1
Physician Decision             2
Arm/Group Title Atezolizumab
Hide Arm/Group Description Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of adjuvant atezolizumab.
Overall Number of Baseline Participants 181
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 181 participants
65.1  (9.23)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 181 participants
Female
93
  51.4%
Male
88
  48.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 181 participants
Hispanic or Latino
8
   4.4%
Not Hispanic or Latino
159
  87.8%
Unknown or Not Reported
14
   7.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 181 participants
American Indian or Alaska Native
0
   0.0%
Asian
9
   5.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
13
   7.2%
White
145
  80.1%
More than one race
0
   0.0%
Unknown or Not Reported
14
   7.7%
1.Primary Outcome
Title Percentage of Participants With Major Pathologic Response (MPR)
Hide Description Major pathologic response (defined as ≤ 10% of viable tumor cells), scored by a pathologist, based on surgical resection as defined by prior studies.
Time Frame After surgery (approximately 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy population included NSCLC participants who have received surgery after neoadjuvant treatment with Atezolizumab, received at least one dose of the study drug, and who do not have EGFR or ALK mutant tumors.
Arm/Group Title Atezolizumab
Hide Arm/Group Description:
Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of adjuvant atezolizumab.
Overall Number of Participants Analyzed 144
Measure Type: Number
Unit of Measure: Percentage of Participants
20.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Other/Percentage
Estimated Value 20.8
Confidence Interval (1-Sided) 95%
15.413
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Hide Description Objective response rate is the proportion of participants who are objective responders (Complete Response and Partial Response are considered as responders, Stable Disease, Progressive Disease and Not Evaluable are considered as nonresponders) in the PD-L1 positive (TC123IC123) and negative (TC0IC0) groups.
Time Frame After surgery (approximately 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy population included NSCLC participants who have received surgery after neoadjuvant treatment with Atezolizumab, received at least one dose of the study drug, and who do not have EGFR or ALK mutant tumors. Participants with missing pre-surgery or assessment, or unknown PD-L1 were excluded.
Arm/Group Title Atezolizumab
Hide Arm/Group Description:
Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of adjuvant atezolizumab.
Overall Number of Participants Analyzed 143
Measure Type: Number
Unit of Measure: Percentage of participants
PD-L1 Positive Group Number Analyzed 60 participants
13.3
PD-L1 Negative Group Number Analyzed 52 participants
1.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0358
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 11.410
Confidence Interval (1-Sided) 80%
5.279
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Major Pathologic Response Rates For Programmed Death Ligand 1 (PD-L1)-Positive Versus PD-L1-Negative Participants
Hide Description Major pathologic response (defined as ≤ 10% of viable tumor cells), scored by a pathologist, based on surgical resection as defined by prior studies.
Time Frame After surgery (approximately 10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy population included NSCLC participants who have received surgery after neoadjuvant treatment with Atezolizumab, received at least one dose of the study drug, and who do not have EGFR or ALK mutant tumors. Participants with missing MPR assessment, or unknown PD-L1 status were excluded.
Arm/Group Title Atezolizumab
Hide Arm/Group Description:
Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of adjuvant atezolizumab.
Overall Number of Participants Analyzed 138
Measure Type: Number
Unit of Measure: Percentage of participants
PD-L1 Positive Group Number Analyzed 57 participants
29.8
PD-L1 Negative Group Number Analyzed 52 participants
13.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atezolizumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0395
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 16.363
Confidence Interval (1-Sided) 80%
6.509
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame From Baseline until 90 days after end of treatment (approximately 16.5 months overall)
Outcome Measure Data Not Reported
Time Frame From the first study drug to the data cutoff date: 23 Oct 2020 (up to approximately 42 months)
Adverse Event Reporting Description The Safety Population included all enrolled NSCLC participants who have received any dose of study drug.
 
Arm/Group Title Atezolizumab
Hide Arm/Group Description Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of adjuvant atezolizumab.
All-Cause Mortality
Atezolizumab
Affected / at Risk (%)
Total   31/181 (17.13%)    
Hide Serious Adverse Events
Atezolizumab
Affected / at Risk (%) # Events
Total   62/181 (34.25%)    
Blood and lymphatic system disorders   
Anaemia † 1  1/181 (0.55%)  1
Cardiac disorders   
Acute myocardial infarction † 1  1/181 (0.55%)  1
Atrial fibrillation † 1  3/181 (1.66%)  4
Cardiac arrest † 1  1/181 (0.55%)  1
Cardiac failure acute † 1  1/181 (0.55%)  2
Gastrointestinal disorders   
Diarrhoea † 1  1/181 (0.55%)  1
Gastrointestinal haemorrhage † 1  1/181 (0.55%)  1
Ileus † 1  1/181 (0.55%)  1
Nausea † 1  1/181 (0.55%)  1
Pancreatitis † 1  1/181 (0.55%)  1
General disorders   
Influenza like illness † 1  2/181 (1.10%)  2
Non-cardiac chest pain † 1  1/181 (0.55%)  1
Pyrexia † 1  5/181 (2.76%)  5
Sudden death † 1  1/181 (0.55%)  1
Infections and infestations   
Diverticulitis † 1  1/181 (0.55%)  1
Empyema † 1  2/181 (1.10%)  2
Influenza † 1  1/181 (0.55%)  1
Pneumonia † 1  8/181 (4.42%)  9
Sepsis † 1  2/181 (1.10%)  2
Tooth infection † 1  1/181 (0.55%)  1
Upper respiratory tract infection † 1  1/181 (0.55%)  1
Injury, poisoning and procedural complications   
Foot fracture † 1  1/181 (0.55%)  1
Investigations   
Blood creatine phosphokinase increased † 1  1/181 (0.55%)  1
Blood potassium increased † 1  1/181 (0.55%)  1
Metabolism and nutrition disorders   
Dehydration † 1  1/181 (0.55%)  1
Failure to thrive † 1  1/181 (0.55%)  1
Hyponatraemia † 1  1/181 (0.55%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Lung neoplasm malignant † 1  1/181 (0.55%)  1
Non-small cell lung cancer † 1  1/181 (0.55%)  1
Tongue neoplasm malignant stage unspecified † 1  1/181 (0.55%)  1
Nervous system disorders   
Cerebrovascular accident † 1  1/181 (0.55%)  1
Dizziness † 1  1/181 (0.55%)  1
Ischaemic stroke † 1  1/181 (0.55%)  1
Seizure † 1  1/181 (0.55%)  1
Syncope † 1  1/181 (0.55%)  1
Product Issues   
Device leakage † 1  1/181 (0.55%)  1
Psychiatric disorders   
Anxiety † 1  1/181 (0.55%)  1
Delirium † 1  1/181 (0.55%)  1
Renal and urinary disorders   
Acute kidney injury † 1  1/181 (0.55%)  1
Azotaemia † 1  1/181 (0.55%)  1
Urinary retention † 1  1/181 (0.55%)  1
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure † 1  1/181 (0.55%)  1
Bronchopleural fistula † 1  1/181 (0.55%)  1
Dyspnoea † 1  5/181 (2.76%)  5
Haemoptysis † 1  2/181 (1.10%)  2
Haemothorax † 1  1/181 (0.55%)  1
Hypoxia † 1  2/181 (1.10%)  2
Pleural effusion † 1  1/181 (0.55%)  1
Pneumonitis † 1  7/181 (3.87%)  8
Pneumothorax † 1  3/181 (1.66%)  3
Pulmonary air leakage † 1  3/181 (1.66%)  3
Pulmonary embolism † 1  1/181 (0.55%)  1
Pulmonary haemorrhage † 1  1/181 (0.55%)  1
Respiratory distress † 1  1/181 (0.55%)  1
Respiratory failure † 1  2/181 (1.10%)  2
Vocal cord dysfunction † 1  1/181 (0.55%)  1
Skin and subcutaneous tissue disorders   
Subcutaneous emphysema † 1  1/181 (0.55%)  1
Vascular disorders   
Hypotension † 1  1/181 (0.55%)  1
1
Term from vocabulary, MedDRA version 23
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atezolizumab
Affected / at Risk (%) # Events
Total   168/181 (92.82%)    
Blood and lymphatic system disorders   
Anaemia † 1  18/181 (9.94%)  20
Gastrointestinal disorders   
Constipation † 1  39/181 (21.55%)  44
Diarrhoea † 1  31/181 (17.13%)  37
Nausea † 1  41/181 (22.65%)  50
Vomiting † 1  18/181 (9.94%)  21
General disorders   
Chills † 1  15/181 (8.29%)  16
Fatigue † 1  79/181 (43.65%)  94
Non-cardiac chest pain † 1  11/181 (6.08%)  11
Oedema peripheral † 1  14/181 (7.73%)  19
Pain † 1  10/181 (5.52%)  15
Pyrexia † 1  26/181 (14.36%)  27
Infections and infestations   
Upper respiratory tract infection † 1  11/181 (6.08%)  12
Urinary tract infection † 1  12/181 (6.63%)  14
Injury, poisoning and procedural complications   
Infusion related reaction † 1  15/181 (8.29%)  17
Procedural pain † 1  54/181 (29.83%)  56
Investigations   
Alanine aminotransferase increased † 1  14/181 (7.73%)  15
Aspartate aminotransferase increased † 1  15/181 (8.29%)  16
Weight decreased † 1  12/181 (6.63%)  14
Metabolism and nutrition disorders   
Decreased appetite † 1  37/181 (20.44%)  40
Dehydration † 1  12/181 (6.63%)  13
Hyperkalaemia † 1  10/181 (5.52%)  11
Hyponatraemia † 1  18/181 (9.94%)  22
Musculoskeletal and connective tissue disorders   
Arthralgia † 1  25/181 (13.81%)  34
Back pain † 1  21/181 (11.60%)  22
Musculoskeletal chest pain † 1  10/181 (5.52%)  11
Musculoskeletal pain † 1  11/181 (6.08%)  12
Nervous system disorders   
Dizziness † 1  21/181 (11.60%)  22
Dysgeusia † 1  10/181 (5.52%)  11
Headache † 1  30/181 (16.57%)  34
Peripheral sensory neuropathy † 1  12/181 (6.63%)  14
Psychiatric disorders   
Anxiety † 1  15/181 (8.29%)  15
Insomnia † 1  20/181 (11.05%)  20
Respiratory, thoracic and mediastinal disorders   
Cough † 1  35/181 (19.34%)  39
Dyspnoea † 1  41/181 (22.65%)  44
Hypoxia † 1  10/181 (5.52%)  11
Nasal congestion † 1  12/181 (6.63%)  14
Pleural effusion † 1  10/181 (5.52%)  10
Pneumothorax † 1  12/181 (6.63%)  12
Productive cough † 1  10/181 (5.52%)  12
Wheezing † 1  11/181 (6.08%)  13
Skin and subcutaneous tissue disorders   
Dry skin † 1  18/181 (9.94%)  19
Pruritus † 1  26/181 (14.36%)  28
Rash maculo-papular † 1  15/181 (8.29%)  21
Vascular disorders   
Hypertension † 1  13/181 (7.18%)  15
Hypotension † 1  12/181 (6.63%)  12
1
Term from vocabulary, MedDRA version 23
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Genentech
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02927301    
Other Study ID Numbers: ML39236
First Submitted: October 5, 2016
First Posted: October 7, 2016
Results First Submitted: April 23, 2021
Results First Posted: May 17, 2021
Last Update Posted: May 17, 2021