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)
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Trastuzumab Emtansine
Intervention description: 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.
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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)