Trial Outcomes & Findings for A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor (HER)2 Immunohistochemistry (IHC)-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (NCT NCT02289833)

Last Updated: 2019-08-07

Results Overview

Objective response is defined as a complete response (CR) or partial response (PR) determined on two consecutive assessments ≥ 4 weeks apart, based on investigator assessment according to RECIST, Version 1.1. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeters (mm). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months)

Results posted on

2019-08-07

Participant Flow

Subjects were screened centrally for HER2 status, using archived tumor specimens from previously collected tissue, if available.

Participant milestones

Participant milestones
Measure	Cohort IHC2+ Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Overall Study STARTED	29	20
Overall Study COMPLETED	2	3
Overall Study NOT COMPLETED	27	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort IHC2+ Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Overall Study Study discontinuation	0	1
Overall Study Lost to Follow-up	4	0
Overall Study Death	23	16

Baseline Characteristics

A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor (HER)2 Immunohistochemistry (IHC)-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort IHC2+ n=29 Participants Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Total n=49 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 10.3 • n=5 Participants	61.4 years STANDARD_DEVIATION 8.6 • n=7 Participants	62.4 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants With Objective Response as Per Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1)	0 percentage of participants Interval 0.0 to 11.9	20.0 percentage of participants Interval 5.7 to 43.7

SECONDARY outcome

Timeframe: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug. Data are reported for participants with events.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants Who Died	79.3 percentage of participants	80.0 percentage of participants

SECONDARY outcome

Timeframe: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug. Data are reported for participants with events.

OS is defined as the time from first study drug administration to death from any cause.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Overall Survival (OS)	12.2 months Interval 3.8 to 23.6	13.7 months Interval 4.1 to 33.0

SECONDARY outcome

Timeframe: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug.

PFS is defined as the time from first study drug administration to first documented disease progression, based on investigator assessment using RECIST, v1.1, or death from any cause during the study, whichever occurs first. Disease progression is defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death	100 percentage of participants	95.0 percentage of participants

SECONDARY outcome

Timeframe: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug. Data are reported for participants with events.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1	2.6 months Interval 1.4 to 2.8	2.7 months Interval 1.4 to 8.3

SECONDARY outcome

Timeframe: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug. Data are reported for participants with response.

DOR is defined as the time from the initial documentation of response (CR or PR using RECIST, v1.1) to documented disease progression using RECIST v1.1 or death from any cause during the study. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=4 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1	—	75.0 percentage of participants Interval 2.9 to 8.3

SECONDARY outcome

Timeframe: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug. Data are reported for participants with response.

DoR is defined as the time from the initial documentation of response (CR or PR using RECIST, v1.1) to documented disease progression using RECIST v1.1 or death from any cause during the study. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=4 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Duration of Objective Response (DOR) Assessed According to RECIST v1.1	—	7.3 months Interval 2.9 to The upper limit confidence interval was not calculable due to the low number of participants with events.

SECONDARY outcome

Timeframe: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

Population: The efficacy-evaluable population included participants who received at least one dose of study drug.

Clinical benefit is defined as having a CR or PR or stable disease (using RECIST, v1.1) at 6 months. Participants with no post-baseline response assessment are considered as experiencing no clinical benefit. CR: disappearance of all target lesions; and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum while in the study. Disease progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1	6.9 percentage of participants Interval 0.85 to 22.77	30.0 percentage of participants Interval 11.89 to 54.28

SECONDARY outcome

Timeframe: From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months)

Population: The safety-evaluable population included participants who received at least one dose of study treatment.

An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, whether or not considered related to the study drug. A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=29 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 Participants Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) AEs	93.1 percentage of participants	95.0 percentage of participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) SAEs	17.2 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycles 1 and 3 (one cycle=21 days); at treatment discontinuation/early termination, up to primary analysis, approx. 22 months

Population: The pharmacokinetic (PK) population included participants who had received at least one dose of study treatment and had at least one serum or plasma concentration result available at clinical data cut-off. Data are reported for evaluable participants.

Cmax is the 0-21 day maximum observed concentration of a drug and was measured in blood serum.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=44 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab Trastuzumab Emtansine	78.7 micrograms per milliliter (ug/mL) Standard Deviation 19.6	—
Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab	79.9 micrograms per milliliter (ug/mL) Standard Deviation 21.3	—

SECONDARY outcome

Timeframe: Pre-dose & 30 minutes (min) post-infusion (inf.) on Day (D) 1 of Cycles (C) 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D1 of C2 & D1 of C 4 (C=21 D); at discontin./termination, up to primary analysis, approx. 22 months

AUC (from zero to infinity) represents the total drug exposure over time in blood serum.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=4 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
AUCinf for Trastuzumab Emtansine and Total Trastuzumab Trastuzumab Emtansine	324 days times ug/mL (day* ug/mL) Standard Deviation 49.9	—
AUCinf for Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab	436 days times ug/mL (day* ug/mL) Standard Deviation 83.4	—

SECONDARY outcome

Timeframe: Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin./early termination, up to primary analysis, approx. 22 months

t1/2 is the time required for the drug serum concentration to be reduced to half.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=4 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab Trastuzumab Emtansine	3.2 days Standard Deviation 0.51	—
Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab	5.6 days Standard Deviation 1.14	—

SECONDARY outcome

Timeframe: Pre-dose & 30 minutes (min) post-infusion (inf.) on D1 of C1 & 3; post- inf. on D2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months

Vss is the volume of distribution of study drug at steady state.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=4 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab Trastuzumab Emtansine	51.1 milliliters kilogram (mL/kg) Standard Deviation 1.81	—
Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab	60.7 milliliters kilogram (mL/kg) Standard Deviation 4.23	—

SECONDARY outcome

Timeframe: Pre-dose & 30 minutes (min) post-infusion (inf.) on D 1 of C 1 & 3; post- inf. on D 2, 3, 4 or 5, 8, & 15 of C 1, & pre- inf. on D 1 of C 2 & D 1 of C 4 (C=21 days); at treatment discontin/early termination, up to primary analysis, approx. 22 months

CL is a measure of the body's elimination of a drug from blood serum over time.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=4 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab	8.54 mL/day/kg Standard Deviation 1.99	—
Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab Trastuzumab Emtansine	11.35 mL/day/kg Standard Deviation 1.99	—

SECONDARY outcome

Timeframe: Pre-dose (within 2 days) and 30 minutes (min) after end of infusion (infusion length= 100 min or less) on Day 1 of Cycle 1 (one cycle=21 days); at treatment discontinuation/early termination,up to primary analysis, approx. 22 months

Cmax is the maximum observed concentration of a drug and was measured in blood plasma.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=34 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)	4.3 nanograms per milliliter (ng/mL) Standard Deviation 3.36	—

SECONDARY outcome

Timeframe: Pre-dose (within 2 days) on Day 1 of Cycles 1 and 3; at treatment discontinuation/early termination,up to primary analysis, approx. 22 months

The presence of ADAs in blood serum is an indication of the body's immune response to a drug.

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Analysis Group n=39 Participants Participants with HER2 IHC2 or IHC3-positive (IHC 2+ or IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)	0 percentage of participants	—

Adverse Events

Cohort IHC2+

Serious events: 5 serious events

Other events: 24 other events

Deaths: 23 deaths

Cohort IHC3+

Serious events: 5 serious events

Other events: 19 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Cohort IHC2+ n=29 participants at risk Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 participants at risk Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
Gastrointestinal disorders Abdominal pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Constipation	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Bronchitis	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Lower respiratory tract infection	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Lung infection	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Pneumonia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Seizure	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Psychiatric disorders Confusional state	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Influenza	3.4% 1/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort IHC2+ n=29 participants at risk Participants with HER2 IHC2-positive (IHC 2+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.	Cohort IHC3+ n=20 participants at risk Participants with HER2 IHC3-positive (IHC 3+) locally advanced or metastatic NSCLC, who had received at least one prior platinum-based chemotherapy regimen, will receive trastuzumab emtansine.
General disorders Fatigue	34.5% 10/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
General disorders Asthenia	17.2% 5/29 • From baseline to study completion (approximately 43 months)	20.0% 4/20 • From baseline to study completion (approximately 43 months)
General disorders Chills	3.4% 1/29 • From baseline to study completion (approximately 43 months)	20.0% 4/20 • From baseline to study completion (approximately 43 months)
General disorders Pyrexia	13.8% 4/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
General disorders Chest pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
General disorders Mucosal inflammation	6.9% 2/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
General disorders Malaise	6.9% 2/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
General disorders Oedema peripheral	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
General disorders Influenza like illness	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
General disorders Non-cardiac chest pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
General disorders Oedema	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Cough	24.1% 7/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	27.6% 8/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/29 • From baseline to study completion (approximately 43 months)	20.0% 4/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.9% 2/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Dysphonia	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Pulmonary pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Metabolism and nutrition disorders Decreased appetite	34.5% 10/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Metabolism and nutrition disorders Hypokalaemia	6.9% 2/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Metabolism and nutrition disorders Hyperglycaemia	6.9% 2/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Nausea	20.7% 6/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Vomiting	10.3% 3/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Dry mouth	13.8% 4/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Constipation	3.4% 1/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Diarrhoea	6.9% 2/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Dyspepsia	3.4% 1/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Abdominal pain	6.9% 2/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Mouth ulceration	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Stomatitis	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Arthralgia	13.8% 4/29 • From baseline to study completion (approximately 43 months)	20.0% 4/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Muscle spasms	3.4% 1/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Muscular weakness	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Myalgia	6.9% 2/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Investigations Aspartate aminotransferase increased	6.9% 2/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Investigations Platelet count decreased	6.9% 2/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Investigations Weight decreased	10.3% 3/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Investigations Alanine aminotransferase increased	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Investigations Blood alkaline phosphatase increased	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Investigations Blood bilirubin increased	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Investigations Lymphocyte count decreased	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Investigations White blood cell count decreased	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Neuropathy peripheral	13.8% 4/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Headache	10.3% 3/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Cerebrovascular accident	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Dizziness	0.00% 0/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Paraesthesia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Nervous system disorders Sciatica	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Pruritus	6.9% 2/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Eczema	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Injury, poisoning and procedural complications Infusion related reaction	10.3% 3/29 • From baseline to study completion (approximately 43 months)	20.0% 4/20 • From baseline to study completion (approximately 43 months)
Injury, poisoning and procedural complications Skin Wound	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Respiratory tract infection	10.3% 3/29 • From baseline to study completion (approximately 43 months)	0.00% 0/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Urinary tract infection	3.4% 1/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Pneumonia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	10.0% 2/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Paronychia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Blood and lymphatic system disorders Anaemia	3.4% 1/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Psychiatric disorders Anxiety	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Psychiatric disorders Depressive symptom	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Psychiatric disorders Insomnia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	15.0% 3/20 • From baseline to study completion (approximately 43 months)
Cardiac disorders Sinus tachycardia	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Reproductive system and breast disorders Metrorrhagia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Vascular disorders Poor venous access	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Blood and lymphatic system disorders Leukocytosis	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Blood and lymphatic system disorders Thrombocytopenia	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Gastrointestinal disorders Odynophagia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
General disorders Mucosal Dryness	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Metabolism and nutrition disorders Iron Deficiency	6.9% 2/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Musculoskeletal and connective tissue disorders Pain in Extremity	3.4% 1/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/29 • From baseline to study completion (approximately 43 months)	5.0% 1/20 • From baseline to study completion (approximately 43 months)