Inclusion Criteria:
- Age >/= 18 years
- 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
- Patients with a known ALK fusion oncogene (must be documented in the patient'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 (e.g., crizotinib). Disease progression or intolerance must be documented
- Patients with a known mutation in the EGFR gene (must be documented in the patient's
chart) must have also experienced disease progression or intolerance with an EGFR TKI
approved for the treatment of EGFR-mutant NSCLC (e.g., gefitinib, erlotinib,
afatinib). Disease progression or intolerance must be documented
- Measurable disease determined as per the Response Evaluation Criteria in Solid Tumors
(RECIST), version 1.1
- Life expectancy >/= 12 weeks
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Left ventricular ejection fraction (LVEF) >/= 50% by either echocardiogram (ECHO) or
multiple-gated acquisition (MUGA)
- Use of highly effective contraception
Exclusion Criteria:
Cancer-Related Criteria
- Any approved anti-cancer therapy </= 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 > 7 days prior to the
first study treatment on Cycle 1, Day 1 (The baseline computed tomography scan must
be completed after discontinuation of TKIs); (2) Hormone-replacement therapy or oral
contraceptives; (3) Anti-emetics, GCS-F, prophylactic antibiotics are allowed
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 of Cycle 1 as
long as a sufficient number of target lesions remain to allow for measurable disease
as per RECIST v1.1.
- Patients who have untreated brain metastases or are symptomatic; patients 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 mg/m2; Epirubicin > 900 mg/m2; Mitoxantrone > 120
mg/m2. If another anthracycline, or more than one anthracycline, has been used, the
cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
- Current peripheral neuropathy of Grade >/= 3 per the National Cancer Institute Common
Toxicity Criteria for Adverse Events (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 (e.g., 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 HIV, hepatitis B, or hepatitis C virus
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both