Clinical trial NCT02289833: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-11-13
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: From Day 1 to disease progression (PD) or death from any cause, up to the clinical cutoff date (approximately 22 months)
Secondary outcomes:
measure: Percentage of Participants Who Died
timeFrame: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)
measure: Overall Survival (OS)
timeFrame: From Day 1 to death from any cause, up to the study completion date (approximately 43 months)
measure: Percentage of Participants With PFS Event of Disease Progression, as Per Investigator Assessment According to RECIST v. 1.1, or Death
timeFrame: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)
measure: Progression-Free Survival (PFS) as Per Investigator Assessment According to RECIST v. 1.1
timeFrame: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)
measure: Percentage of Participants With DOR Event of Disease Progression, Assessed According to RECIST v1.1
timeFrame: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)
measure: Duration of Objective Response (DOR) Assessed According to RECIST v1.1
timeFrame: From first documented objective response to PD or death from any cause, up to the study completion date (approximately 43 months)
measure: Percentage of Participants With Clinical Benefit as Per Investigator Assessment According to RECIST, v1.1
timeFrame: From Day 1 to PD or death from any cause, up to the study completion date (approximately 43 months)
measure: Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: From Day 1 to 30 days after last dose of study drug, up to the study completion date (approximately 43 months)
measure: Maximum Observed Concentration (Cmax) for Trastuzumab Emtansine and Total Trastuzumab
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
measure: AUCinf for Trastuzumab Emtansine and Total Trastuzumab
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
measure: Elimination Half-Life (t1/2) for Trastuzumab Emtansine and Total Trastuzumab
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
measure: Volume of Distribution (Vss) for Trastuzumab Emtansine and Total Trastuzumab
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
measure: Clearance (CL) for Trastuzumab Emtansine and Total Trastuzumab
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
measure: Maximum Observed Concentration (Cmax) for N2'- Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)
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
measure: Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
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
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Berlin
country: Germany
facility: HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie
city: Düsseldorf
country: Germany
facility: Kaiserswerther Diakonie Florence Nightingale-Krankenh. Tagesklinik f.Onkologie
city: Gauting
country: Germany
facility: Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Parma
country: Italy
facility: Azienda Ospedaliera Univ Parma; Dept Oncologia Medica
state: Emilia-Romagna
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia
city: Lausanne
country: Switzerland
facility: CHUV; Departement d'Oncologie
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: