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Study of Patritumab in Combination With Erlotinib in Subjects With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). (HER3-Lung) (HER3-Lung)

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ClinicalTrials.gov Identifier: NCT02134015
Recruitment Status : Terminated (Pre-defined criteria for continuation were not reached)
First Posted : May 8, 2014
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Lung Cancer
Non-small Cell Lung Cancer
Interventions Drug: Patritumab
Drug: Erlotinib
Drug: Placebo
Enrollment 145
Recruitment Details The first participant was randomized on 11 Jun 2014, and the last patient's last visit occurred on 11 Nov 2016. All randomized participants received study treatment and were included in both the Full Analysis Set and the Safety Analysis Set.
Pre-assignment Details Of 537 patients screened, a total of 145 patients were randomized into this trial in 9 countries: United States (26 at 12 sites), Spain (19 at 5 sites), Hungary (18 at 4 sites), Italy (20 at 6 sites), Great Britain (11 at 5 sites), Poland (30 at 3 sites), Germany (16 at 6 sites), Canada (2 at 1 site) and Belgium (3 at 1 site).
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description Placebo infusion every 3 weeks and oral erlotinib 150 mg/day Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Period Title: Overall Study
Started 71 74
Completed 0 0
Not Completed 71 74
Reason Not Completed
Protocol Violation             0             1
Death             2             1
Reason not provided             1             2
Clinical progression             14             7
Progressive disease (per RECIST 1.1)             40             43
Study terminated by sponsor             2             3
Adverse Event             9             10
Withdrawal by Subject             3             7
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib Total
Hide Arm/Group Description Placebo infusion every 3 weeks and oral erlotinib 150 mg/day Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day Total of all reporting groups
Overall Number of Baseline Participants 71 74 145
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
38
  53.5%
40
  54.1%
78
  53.8%
>=65 years
33
  46.5%
34
  45.9%
67
  46.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 74 participants 145 participants
63.3  (9.15) 63.9  (8.25) 63.6  (8.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
Female
22
  31.0%
30
  40.5%
52
  35.9%
Male
49
  69.0%
44
  59.5%
93
  64.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
Hispanic or Latino
5
   7.0%
1
   1.4%
6
   4.1%
Not Hispanic or Latino
59
  83.1%
66
  89.2%
125
  86.2%
Unknown or Not Reported
7
   9.9%
7
   9.5%
14
   9.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
American Indian or Alaska Native
0
   0.0%
1
   1.4%
1
   0.7%
Asian
0
   0.0%
1
   1.4%
1
   0.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
   2.7%
2
   1.4%
White
71
 100.0%
70
  94.6%
141
  97.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Histology subtype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
Adenocarcinoma
39
  54.9%
40
  54.1%
79
  54.5%
Squamous
28
  39.4%
28
  37.8%
56
  38.6%
Large Cell
1
   1.4%
1
   1.4%
2
   1.4%
Other
3
   4.2%
5
   6.8%
8
   5.5%
Histology subtype (for randomization)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
Adenocarcinoma
38
  53.5%
40
  54.1%
78
  53.8%
Squamous-cell carcinoma/Not otherwise specified
33
  46.5%
34
  45.9%
67
  46.2%
Eastern Cooperative Oncology Group (ECOG) Score  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
0 - Fully Active
24
  33.8%
25
  33.8%
49
  33.8%
1 - Restricted in Physically Strenuous Activity
47
  66.2%
49
  66.2%
96
  66.2%
Heregulin (HRG) expression from Interactive Web/Voice Response System (IXRS)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 74 participants 145 participants
HRG High
48
  67.6%
47
  63.5%
95
  65.5%
HRG Low
23
  32.4%
27
  36.5%
50
  34.5%
1.Primary Outcome
Title Part A: Progression Free Survival (PFS) in Heregulin-high Participants
Hide Description

PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.

Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.

Time Frame by trial termination (at 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 48 47
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: months
2.7
(1.7 to 2.9)
1.9
(1.4 to 3.5)
2.Primary Outcome
Title Part A: Progression Free Survival (PFS) in Heregulin-low Participants
Hide Description

PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.

Kaplan-Meier Estimate. Confidence interval (CI) for median was computed using the Brookmeyer-Crowley method. 80% confidence interval is included in the data table.

Time Frame by trial termination (at 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 23 27
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: months
2.8
(1.4 to 4.2)
1.5
(1.4 to 2.7)
3.Primary Outcome
Title Part B: Overall Survival
Hide Description Percentage of participants still alive at the end of Part B
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were analyzed for Part B endpoints because the trial was terminated at the end of Part A.
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Part A: Overall Survival in HRG High Participants
Hide Description Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial
Time Frame by trial termination (at 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 48 47
Measure Type: Count of Participants
Unit of Measure: Participants
15
  31.3%
17
  36.2%
5.Secondary Outcome
Title Part A: Key Secondary Efficacy Endpoint: Overall Survival in HRG Low Participants
Hide Description Key secondary efficacy endpoint: Percentage of participants who survived for the length of the trial
Time Frame by trial termination (at 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 23 27
Measure Type: Count of Participants
Unit of Measure: Participants
7
  30.4%
8
  29.6%
6.Secondary Outcome
Title Part B: Key Secondary Efficacy Endpoint: PFS, TTD
Hide Description PFS is defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression (TTD, as per RECIST Version 1.1 per investigator assessment) or death resulting from any cause.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were analyzed for Part B endpoints because the trial was terminated at the end of Part A.
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Part A: Objective Response Rate (ORR) in HRG High Participants
Hide Description

Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response (CR) or partial response (PR)

Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response [in the order of CR, PR, stable disease (SD), and progressive disease (PD)] among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.

Time Frame by trial termination (at 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable participants in the full analysis set
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 48 46
Measure Type: Count of Participants
Unit of Measure: Participants
3
   6.3%
1
   2.2%
8.Secondary Outcome
Title Part A: Objective Response Rate (ORR) in HRG Low Participants
Hide Description

Key secondary efficacy endpoint: Objective response is defined as percentage of participants achieving complete response or partial response

Denominator for percentages is the number of subjects with measurable disease in the full analysis set. The best overall response is the best response (in the order of CR, PR, SD, and PD) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no post-baseline tumor assessment or all post-baseline tumor assessments with overall response being Inevaluable captured in the CRF, the best overall response is classified as Inevaluable.

Time Frame by trial termination (at 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable participants in the full analysis set
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description:
Placebo infusion every 3 weeks and oral erlotinib 150 mg/day
Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
Overall Number of Participants Analyzed 22 27
Measure Type: Count of Participants
Unit of Measure: Participants
3
  13.6%
1
   3.7%
Time Frame 53 days after the last dose of patritumab/placebo or 30 days after the last dose of erlotinib, whichever is later (within the length of the trial, which was 2 years, 7 months)
Adverse Event Reporting Description Treatment emergent (TE) adverse events (AEs) are reported for patritumab only. If relatedness is missing, the AE is counted as related to patritumab.
 
Arm/Group Title Placebo + Erlotinib Patritumab + Erlotinib
Hide Arm/Group Description Placebo infusion every 3 weeks and oral erlotinib 150 mg/day Infusion of Patritumab (loading dose of 18 mg/kg, followed by 9 mg/kg every 3 weeks) and oral erlotinib 150 mg/day
All-Cause Mortality
Placebo + Erlotinib Patritumab + Erlotinib
Affected / at Risk (%) Affected / at Risk (%)
Total   5/71 (7.04%)      5/74 (6.76%)    
Hide Serious Adverse Events
Placebo + Erlotinib Patritumab + Erlotinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/71 (40.85%)      27/74 (36.49%)    
Blood and lymphatic system disorders     
Anaemia  1  1/71 (1.41%)  0/74 (0.00%) 
Cardiac disorders     
Cardiac failure  1  1/71 (1.41%)  0/74 (0.00%) 
Cardiac tamponade  1  0/71 (0.00%)  1/74 (1.35%) 
Cardiopulmonary failure  1  0/71 (0.00%)  1/74 (1.35%) 
Tachycardia  1  0/71 (0.00%)  1/74 (1.35%) 
Gastrointestinal disorders     
Diarrhoea  1  0/71 (0.00%)  2/74 (2.70%) 
Aphagia  1  1/71 (1.41%)  0/74 (0.00%) 
Dysphagia  1  1/71 (1.41%)  0/74 (0.00%) 
Large intestinal obstruction  1  0/71 (0.00%)  1/74 (1.35%) 
Swollen tongue  1  0/71 (0.00%)  1/74 (1.35%) 
General disorders     
General physical health deterioration  1  1/71 (1.41%)  2/74 (2.70%) 
Asthenia  1  1/71 (1.41%)  0/74 (0.00%) 
Pain  1  0/71 (0.00%)  1/74 (1.35%) 
Hepatobiliary disorders     
Cholecystitis  1  1/71 (1.41%)  0/74 (0.00%) 
Infections and infestations     
Pneumonia  1  3/71 (4.23%)  1/74 (1.35%) 
Bronchitis  1  1/71 (1.41%)  0/74 (0.00%) 
Empyema  1  1/71 (1.41%)  0/74 (0.00%) 
Lung abscess  1  1/71 (1.41%)  0/74 (0.00%) 
Neutropenic sepsis  1  0/71 (0.00%)  1/74 (1.35%) 
Respiratory tract infection  1  1/71 (1.41%)  0/74 (0.00%) 
Staphylococcal sepsis  1  0/71 (0.00%)  1/74 (1.35%) 
Injury, poisoning and procedural complications     
Craniocerebral injury  1  0/71 (0.00%)  1/74 (1.35%) 
Investigations     
Alanine aminotransferase increased  1  0/71 (0.00%)  1/74 (1.35%) 
Aspartate aminotransferase increased  1  0/71 (0.00%)  1/74 (1.35%) 
C-reactive protein increased  1  0/71 (0.00%)  1/74 (1.35%) 
Electrocardiogram QT prolonged  1  0/71 (0.00%)  1/74 (1.35%) 
Hepatic enzyme increased  1  0/71 (0.00%)  1/74 (1.35%) 
Transaminases increased  1  1/71 (1.41%)  0/74 (0.00%) 
Metabolism and nutrition disorders     
Hypercalcaemia  1  1/71 (1.41%)  1/74 (1.35%) 
Hypokalaemia  1  0/71 (0.00%)  1/74 (1.35%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  1/71 (1.41%)  0/74 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  1/71 (1.41%)  0/74 (0.00%) 
Tumour pain  1  1/71 (1.41%)  0/74 (0.00%) 
Nervous system disorders     
Dizziness  1  1/71 (1.41%)  0/74 (0.00%) 
Headache  1  0/71 (0.00%)  1/74 (1.35%) 
Transient ischaemic attack  1  0/71 (0.00%)  1/74 (1.35%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  3/71 (4.23%)  5/74 (6.76%) 
Haemoptysis  1  0/71 (0.00%)  2/74 (2.70%) 
Respiratory failure  1  1/71 (1.41%)  2/74 (2.70%) 
Acute respiratory failure  1  1/71 (1.41%)  0/74 (0.00%) 
Chronic obstructive pulmonary disease  1  1/71 (1.41%)  0/74 (0.00%) 
Hydropneumothorax  1  0/71 (0.00%)  1/74 (1.35%) 
Pleural effusion  1  1/71 (1.41%)  1/74 (1.35%) 
Pneumonitis  1  1/71 (1.41%)  0/74 (0.00%) 
Pneumothorax  1  1/71 (1.41%)  1/74 (1.35%) 
Pulmonary embolism  1  1/71 (1.41%)  1/74 (1.35%) 
Pulmonary haemorrhage  1  1/71 (1.41%)  0/74 (0.00%) 
Respiratory arrest  1  0/71 (0.00%)  1/74 (1.35%) 
Skin and subcutaneous tissue disorders     
Eczema  1  1/71 (1.41%)  0/74 (0.00%) 
Skin disorder  1  1/71 (1.41%)  0/74 (0.00%) 
Skin fissures  1  0/71 (0.00%)  1/74 (1.35%) 
Vascular disorders     
Deep vein thrombosis  1  1/71 (1.41%)  1/74 (1.35%) 
1
Term from vocabulary, MedDRA (16.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Erlotinib Patritumab + Erlotinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   66/71 (92.96%)      68/74 (91.89%)    
Blood and lymphatic system disorders     
Anaemia  1  4/71 (5.63%)  5 6/74 (8.11%)  10
Gastrointestinal disorders     
Diarrhoea  1  22/71 (30.99%)  41 39/74 (52.70%)  62
Nausea  1  16/71 (22.54%)  18 15/74 (20.27%)  19
Stomatitis  1  2/71 (2.82%)  2 11/74 (14.86%)  18
Vomiting  1  7/71 (9.86%)  8 10/74 (13.51%)  13
Constipation  1  2/71 (2.82%)  2 9/74 (12.16%)  9
Dyspepsia  1  3/71 (4.23%)  3 5/74 (6.76%)  7
General disorders     
Fatigue  1  17/71 (23.94%)  23 11/74 (14.86%)  12
Oedema peripheral  1  6/71 (8.45%)  6 5/74 (6.76%)  5
Asthenia  1  5/71 (7.04%)  6 5/74 (6.76%)  5
Chest pain  1  4/71 (5.63%)  5 2/74 (2.70%)  2
Infections and infestations     
Paronychia  1  3/71 (4.23%)  4 7/74 (9.46%)  16
Rhinitis  1  0/71 (0.00%)  0 4/74 (5.41%)  4
Investigations     
Weight decreased  1  8/71 (11.27%)  9 10/74 (13.51%)  11
Metabolism and nutrition disorders     
Decreased appetite  1  13/71 (18.31%)  16 17/74 (22.97%)  21
Hypomagnesaemia  1  4/71 (5.63%)  7 7/74 (9.46%)  17
Hypokalaemia  1  1/71 (1.41%)  1 6/74 (8.11%)  6
Dehydration  1  1/71 (1.41%)  1 4/74 (5.41%)  4
Nervous system disorders     
Dizziness  1  5/71 (7.04%)  5 0/74 (0.00%)  0
Dysgeusia  1  3/71 (4.23%)  3 4/74 (5.41%)  4
Psychiatric disorders     
Insomnia  1  3/71 (4.23%)  3 4/74 (5.41%)  4
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  16/71 (22.54%)  21 9/74 (12.16%)  11
Cough  1  11/71 (15.49%)  11 10/74 (13.51%)  14
Haemoptysis  1  5/71 (7.04%)  7 5/74 (6.76%)  7
Dysphonia  1  0/71 (0.00%)  0 4/74 (5.41%)  4
Skin and subcutaneous tissue disorders     
Rash  1  26/71 (36.62%)  46 28/74 (37.84%)  57
Dermatitis acneiform  1  6/71 (8.45%)  7 13/74 (17.57%)  23
Dry skin  1  7/71 (9.86%)  7 13/74 (17.57%)  14
Alopecia  1  3/71 (4.23%)  4 6/74 (8.11%)  6
Rash maculo-papular  1  4/71 (5.63%)  4 3/74 (4.05%)  5
Vascular disorders     
Pruritus  1  4/71 (5.63%)  6 6/74 (8.11%)  7
1
Term from vocabulary, MedDRA (16.1)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Leader
Organization: Daiichi Sankyo, Inc.
Phone: 9089926400
EMail: DataSharing@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02134015    
Other Study ID Numbers: U31287-A-U301
2013-004371-12 ( EudraCT Number )
First Submitted: April 8, 2014
First Posted: May 8, 2014
Results First Submitted: November 29, 2017
Results First Posted: January 23, 2018
Last Update Posted: January 23, 2018