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)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02289833
• Collaborator: (none)
• Enrollment: 49
• Locations: 23
• Arms: 2
• Actual Duration (Months): 44.2
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a Phase 2, multicenter study designed to evaluate the efficacy and safety of trastuzumab emtansine administered as a single-agent in participants with HER2-positive (HER2 IHC 2+ or HER2 IHC 3+) advanced or metastatic NSCLC. Participants will be treated with trastuzumab emtansine administered intravenously at a dose of 3.6 milligrams per kilogram (mg/kg) on Day 1 of 21-day cycles until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the Sponsor, whichever occurs first.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Trastuzumab Emtansine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Single-Arm Study of Trastuzumab Emtansine in Patients With HER2 IHC-Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Received At Least One Prior Chemotherapy Regimen
• Actual Study Start Date: Dec 15, 2014
• Actual Primary Completion Date: Oct 25, 2016
• Actual Study Completion Date: Aug 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine will be administered intravenously (IV) at a dose of 3.6 mg/kg on Day 1 of every 21-day cycle until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the sponsor, whichever occurs first.; Other Names: Kadcyla, T-DM1
Experimental: 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.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine will be administered intravenously (IV) at a dose of 3.6 mg/kg on Day 1 of every 21-day cycle until disease progression (as assessed by the investigator), unmanageable toxicity, or study termination by the sponsor, whichever occurs first.; Other Names: Kadcyla, T-DM1

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

1. Percentage of Participants Who Died [From Day 1 to death from any cause, up to the study completion date (approximately 43 months)]

2. Overall Survival (OS) [From Day 1 to death from any cause, up to the study completion date (approximately 43 months)]

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

3. Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death [From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)]

   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.

4. Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1 [From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)]

   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.

5. Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1 [From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)]

   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.

6. Duration of Objective Response (DOR) Assessed According to RECIST v1.1 [From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)]

   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.

7. Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1 [From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)]

   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.

8. Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months)]

   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.

9. Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab [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]

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

10. AUCinf for Trastuzumab Emtansine and Total Trastuzumab [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.

11. Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab [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.

12. Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab [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.

13. Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab [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.

14. Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) [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.

15. Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically documented diagnosis of Stage IIIB not amenable to radical treatment or Stage IV NSCLC (pathological characterization must determine the non-squamous or squamous histological subtype as well as adenocarcinoma subtype classification)

• HER2 status of IHC 2+ or 3+ as determined by a Sponsor-designated central laboratory

• Prior treatment with at least one regimen of platinum-based (cisplatin or carboplatin) chemotherapy in the locally advanced or metastatic setting/recurrent NSCLC with documented disease progression by investigator assessment

• Participants with a known anaplastic lymphoma kinase (ALK) fusion oncogene (must be documented in the participant's chart) must have also experienced disease progression or intolerance with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene NSCLC (for example, crizotinib). Disease progression or intolerance must be documented

• Participants with a known mutation in the epidermal growth factor receptor (EGFR) gene (must be documented in the participant's chart) must have also experienced disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC (for example, gefitinib, erlotinib, afatinib). Disease progression or intolerance must be documented

• Measurable disease determined as per the RECIST v1.1

• Life expectancy of at least (>/=) 12 weeks

• Adequate organ function

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Left ventricular ejection fraction (LVEF) >/= 50 percent (%) by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan

• Use of highly effective contraception

Exclusion Criteria:

Cancer-Related Criteria:

• Any approved anti-cancer therapy less than or equal to (</=) 21 days (including chemotherapy or hormonal therapy) before the first study treatment; the following exceptions are allowed: (1) TKIs approved for the treatment of NSCLC must be discontinued greater than (>) 7 days prior to the first study treatment on D1C1 (The baseline computed tomography [CT] scan must be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral contraceptives; (3) Anti-emetics, Granulocyte-colony stimulating factor (GCS-F), and prophylactic antibiotics according to local standards

• Investigational therapy participation in another clinical study with therapeutic intent </= 21 days before first study treatment

• Previous irradiation is permitted if >/=14 days since the last fraction of radiotherapy have elapsed before the first study treatment on Day 1 as long as a sufficient number of target lesions remain to allow for measurable disease as per RECIST v1.1

• Participants who have untreated brain metastases or are symptomatic; participants with treated brain metastases must have discontinued corticosteroid therapy and not have any neurological symptoms

• History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any excipient of the product

• History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 milligram per meter-square (mg/m^{2); Epirubicin > 900 mg/m}2; Mitoxantrone > 120 mg/m^{2. If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m}2 doxorubicin

• Peripheral neuropathy of Grade >/= 3 per the National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v. 4.0)

• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above

Cardiopulmonary Function Criteria:

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures

• Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy

• Clinical history of active hemoptysis

• Evidence of active pneumonitis during screening

• Current unstable ventricular arrhythmia requiring treatment

• History of symptomatic congestive heart failure (CHF) New York Heart Association (NYHA) classes II-IV

• History of myocardial infarction or unstable angina within 6 months of enrollment

• History of a decrease in LVEF to <50%

General Criteria:

• Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease)

• Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment

• Current pregnancy or lactation

• Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)	Jacksonville	Florida	United States	32256
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514
5	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
6	HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie	Berlin		Germany	14165
7	Kaiserswerther Diakonie Florence Nightingale-Krankenh. Tagesklinik f.Onkologie	Düsseldorf		Germany	40489
8	Asklepios-Fachkliniken Muenchen-Gauting; Onkologie	Gauting		Germany	82131
9	Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II	Halle		Germany	06120
10	Fachklinik für Lungenerkrankungen	Immenhausen		Germany	34376
11	Azienda Ospedaliera Univ Parma; Dept Oncologia Medica	Parma	Emilia-Romagna	Italy	43100
12	Istituto Europeo Di Oncologia	Milano	Lombardia	Italy	20141
13	Seoul National University Hospital	Seoul		Korea, Republic of	03080
14	Asan Medical Center - Oncology	Seoul		Korea, Republic of	05505
15	Medical University of Gdansk	Gdansk		Poland	80-211
16	Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii	Otwock		Poland	05-400
17	Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa		Poland	02-781
18	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
19	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
20	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
21	Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia	Zaragoza		Spain	50009
22	CHUV; Departement d'Oncologie	Lausanne		Switzerland	1011
23	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich		Switzerland	8091

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02289833
• Other Study ID Numbers: BO29389; 2014-001237-83
• First Posted: Nov 13, 2014
• Last Update Posted: Aug 7, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine

Study Results

Participant Flow

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	29	20
COMPLETED	2	3
NOT COMPLETED	27	17

Baseline Characteristics

Arm/Group Title	Cohort IHC2+	Cohort IHC3+	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	29	20	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (10.3)	61.4 (8.6)	62.4 (9.6)
Sex: Female, Male (Count of Participants)
Female	13 44.8%	7 35%	20 40.8%
Male	16 55.2%	13 65%	29 59.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
Number (95% Confidence Interval) [percentage of participants]	0 0%	20.0 100%

2. Secondary Outcome

Title	Percentage of Participants Who Died
Time Frame	From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
Number [percentage of participants]	79.3 273.4%	80.0 400%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from first study drug administration to death from any cause.
Time Frame	From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
Median (95% Confidence Interval) [months]	12.2	13.7

4. Secondary Outcome

Title	Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death
Description	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.
Time Frame	From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
Number [percentage of participants]	100 344.8%	95.0 475%

5. Secondary Outcome

Title	Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1
Description	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.
Time Frame	From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
Median (95% Confidence Interval) [months]	2.6	2.7

6. Secondary Outcome

Title	Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1
Description	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.
Time Frame	From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	0	4
Number [percentage of participants]	75.0 258.6%

7. Secondary Outcome

Title	Duration of Objective Response (DOR) Assessed According to RECIST v1.1
Description	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.
Time Frame	From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	0	4
Median (95% Confidence Interval) [months]	7.3

8. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1
Description	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.
Time Frame	From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
Number (95% Confidence Interval) [percentage of participants]	6.9 23.8%	30.0 150%

9. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description	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.
Time Frame	From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort IHC2+	Cohort IHC3+
Arm/Group Description	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.	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.
Measure Participants	29	20
AEs	93.1 321%	95.0 475%
SAEs	17.2 59.3%	25.0 125%

10. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab
Description	Cmax is the 0-21 day maximum observed concentration of a drug and was measured in blood serum.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pharmacokinetic (PK) Analysis Group
Arm/Group Description	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.
Measure Participants	44
Trastuzumab Emtansine	78.7 (19.6)
Total Trastuzumab	79.9 (21.3)

11. Secondary Outcome

Title	AUCinf for Trastuzumab Emtansine and Total Trastuzumab
Description	AUC (from zero to infinity) represents the total drug exposure over time in blood serum.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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 who consented to intense sampling.

Arm/Group Title	Pharmacokinetic (PK) Analysis Group
Arm/Group Description	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.
Measure Participants	4
Trastuzumab Emtansine	324 (49.9)
Total Trastuzumab	436 (83.4)

12. Secondary Outcome

Title	Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab
Description	t1/2 is the time required for the drug serum concentration to be reduced to half.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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 who consented to intense sampling.

Arm/Group Title	Pharmacokinetic (PK) Analysis Group
Arm/Group Description	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.
Measure Participants	4
Trastuzumab Emtansine	3.2 (0.51)
Total Trastuzumab	5.6 (1.14)

13. Secondary Outcome

Title	Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab
Description	Vss is the volume of distribution of study drug at steady state.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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 who consented to intense sampling.

Arm/Group Title	Pharmacokinetic (PK) Analysis Group
Arm/Group Description	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.
Measure Participants	4
Trastuzumab Emtansine	51.1 (1.81)
Total Trastuzumab	60.7 (4.23)

14. Secondary Outcome

Title	Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab
Description	CL is a measure of the body's elimination of a drug from blood serum over time.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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 who consented to intense sampling.

Arm/Group Title	Pharmacokinetic (PK) Analysis Group
Arm/Group Description	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.
Measure Participants	4
Trastuzumab Emtansine	11.35 (1.99)
Total Trastuzumab	8.54 (1.99)

15. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)
Description	Cmax is the maximum observed concentration of a drug and was measured in blood plasma.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pharmacokinetic (PK) Analysis Group
Arm/Group Description	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.
Measure Participants	34
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	4.3 (3.36)

16. Secondary Outcome

Title	Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
Description	The presence of ADAs in blood serum is an indication of the body's immune response to a drug.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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 with post-dose sample available for ADA analysis.

Arm/Group Title	Anti-drug Antibody Analysis Group
Arm/Group Description	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.
Measure Participants	39
Number [percentage of participants]	0 0%

Adverse Events

Time Frame	From baseline to study completion (approximately 43 months)
Arm/Group Title	Cohort IHC2+		Cohort IHC3+
Arm/Group Description	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.		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.
All Cause Mortality
	Cohort IHC2+		Cohort IHC3+
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/29 (79.3%)		16/20 (80%)
Serious Adverse Events
	Cohort IHC2+		Cohort IHC3+
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)		5/20 (25%)
Gastrointestinal disorders
Abdominal pain	0/29 (0%)		1/20 (5%)
Constipation	1/29 (3.4%)		0/20 (0%)
Infections and infestations
Bronchitis	1/29 (3.4%)		0/20 (0%)
Lower respiratory tract infection	1/29 (3.4%)		0/20 (0%)
Lung infection	1/29 (3.4%)		0/20 (0%)
Pneumonia	0/29 (0%)		1/20 (5%)
Influenza	1/29 (3.4%)		0/20 (0%)
Injury, poisoning and procedural complications
Craniocerebral injury	0/29 (0%)		1/20 (5%)
Subdural haematoma	0/29 (0%)		1/20 (5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/29 (0%)		1/20 (5%)
Nervous system disorders
Seizure	1/29 (3.4%)		0/20 (0%)
Psychiatric disorders
Confusional state	1/29 (3.4%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/29 (3.4%)		1/20 (5%)
Dyspnoea	1/29 (3.4%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Cohort IHC2+		Cohort IHC3+
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/29 (82.8%)		19/20 (95%)
Blood and lymphatic system disorders
Anaemia	1/29 (3.4%)		3/20 (15%)
Leukocytosis	0/29 (0%)		1/20 (5%)
Thrombocytopenia	1/29 (3.4%)		1/20 (5%)
Cardiac disorders
Sinus tachycardia	1/29 (3.4%)		1/20 (5%)
Gastrointestinal disorders
Nausea	6/29 (20.7%)		3/20 (15%)
Vomiting	3/29 (10.3%)		2/20 (10%)
Dry mouth	4/29 (13.8%)		0/20 (0%)
Constipation	1/29 (3.4%)		3/20 (15%)
Diarrhoea	2/29 (6.9%)		2/20 (10%)
Dyspepsia	1/29 (3.4%)		2/20 (10%)
Abdominal pain	2/29 (6.9%)		1/20 (5%)
Abdominal pain upper	0/29 (0%)		2/20 (10%)
Mouth ulceration	0/29 (0%)		1/20 (5%)
Stomatitis	0/29 (0%)		1/20 (5%)
Odynophagia	0/29 (0%)		1/20 (5%)
General disorders
Fatigue	10/29 (34.5%)		3/20 (15%)
Asthenia	5/29 (17.2%)		4/20 (20%)
Chills	1/29 (3.4%)		4/20 (20%)
Pyrexia	4/29 (13.8%)		3/20 (15%)
Chest pain	0/29 (0%)		2/20 (10%)
Mucosal inflammation	2/29 (6.9%)		1/20 (5%)
Malaise	2/29 (6.9%)		0/20 (0%)
Oedema peripheral	1/29 (3.4%)		1/20 (5%)
Influenza like illness	0/29 (0%)		1/20 (5%)
Non-cardiac chest pain	0/29 (0%)		1/20 (5%)
Oedema	0/29 (0%)		1/20 (5%)
Mucosal Dryness	0/29 (0%)		1/20 (5%)
Infections and infestations
Respiratory tract infection	3/29 (10.3%)		0/20 (0%)
Urinary tract infection	1/29 (3.4%)		2/20 (10%)
Pneumonia	0/29 (0%)		2/20 (10%)
Paronychia	0/29 (0%)		1/20 (5%)
Viral Upper Respiratory Tract Infection	0/29 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Infusion related reaction	3/29 (10.3%)		4/20 (20%)
Skin Wound	0/29 (0%)		1/20 (5%)
Investigations
Aspartate aminotransferase increased	2/29 (6.9%)		3/20 (15%)
Platelet count decreased	2/29 (6.9%)		2/20 (10%)
Weight decreased	3/29 (10.3%)		1/20 (5%)
Alanine aminotransferase increased	1/29 (3.4%)		1/20 (5%)
Blood alkaline phosphatase increased	0/29 (0%)		1/20 (5%)
Blood bilirubin increased	0/29 (0%)		1/20 (5%)
Lymphocyte count decreased	0/29 (0%)		1/20 (5%)
White blood cell count decreased	0/29 (0%)		1/20 (5%)
Metabolism and nutrition disorders
Decreased appetite	10/29 (34.5%)		3/20 (15%)
Hypokalaemia	2/29 (6.9%)		2/20 (10%)
Hyperglycaemia	2/29 (6.9%)		0/20 (0%)
Hypomagnesaemia	0/29 (0%)		1/20 (5%)
Hypophosphataemia	0/29 (0%)		1/20 (5%)
Iron Deficiency	2/29 (6.9%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/29 (13.8%)		4/20 (20%)
Muscle spasms	1/29 (3.4%)		2/20 (10%)
Muscular weakness	1/29 (3.4%)		1/20 (5%)
Musculoskeletal chest pain	1/29 (3.4%)		1/20 (5%)
Musculoskeletal pain	1/29 (3.4%)		1/20 (5%)
Myalgia	2/29 (6.9%)		0/20 (0%)
Bone Pain	0/29 (0%)		1/20 (5%)
Pain in Extremity	1/29 (3.4%)		1/20 (5%)
Nervous system disorders
Neuropathy peripheral	4/29 (13.8%)		1/20 (5%)
Headache	3/29 (10.3%)		1/20 (5%)
Cerebrovascular accident	0/29 (0%)		1/20 (5%)
Dizziness	0/29 (0%)		2/20 (10%)
Paraesthesia	0/29 (0%)		1/20 (5%)
Sciatica	0/29 (0%)		1/20 (5%)
Psychiatric disorders
Anxiety	0/29 (0%)		1/20 (5%)
Depressive symptom	0/29 (0%)		1/20 (5%)
Insomnia	0/29 (0%)		3/20 (15%)
Reproductive system and breast disorders
Metrorrhagia	0/29 (0%)		1/20 (5%)
Vaginal haemorrhage	0/29 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	7/29 (24.1%)		3/20 (15%)
Dyspnoea	8/29 (27.6%)		2/20 (10%)
Epistaxis	0/29 (0%)		4/20 (20%)
Pleural effusion	2/29 (6.9%)		1/20 (5%)
Dysphonia	1/29 (3.4%)		1/20 (5%)
Nasal congestion	1/29 (3.4%)		1/20 (5%)
Dyspnoea exertional	0/29 (0%)		1/20 (5%)
Productive cough	0/29 (0%)		1/20 (5%)
Pulmonary pain	0/29 (0%)		1/20 (5%)
Oropharyngeal Pain	0/29 (0%)		1/20 (5%)
Rhinorrhoea	0/29 (0%)		1/20 (5%)
Skin and subcutaneous tissue disorders
Pruritus	2/29 (6.9%)		2/20 (10%)
Rash maculo-papular	0/29 (0%)		3/20 (15%)
Dermatitis acneiform	0/29 (0%)		1/20 (5%)
Eczema	0/29 (0%)		1/20 (5%)
Hyperhidrosis	0/29 (0%)		1/20 (5%)
Petechiae	0/29 (0%)		1/20 (5%)
Alopecia	0/29 (0%)		1/20 (5%)
Onychoclasis	0/29 (0%)		1/20 (5%)
Vascular disorders
Poor venous access	0/29 (0%)		1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.