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Trastuzumab Emtansine in Treating Patients with HER2 Amplified or Mutant Advanced Cancers

Trial Status: Active

This phase II trial studies how well trastuzumab emtansine works in treating patients with human epidermal growth factor receptor 2 (HER2) amplified or HER2 mutant cancers, including lung and bladder, that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Monoclonal antibodies, such as trastuzumab emtansine, may block tumor growth in different ways by targeting certain cells.

Inclusion Criteria

  • Pathologically confirmed advanced solid tumor cancers
  • For cohort 1, documented activating HER2 mutation in lung cancer by Clinical Laboratory Improvement Act (CLIA) laboratory, specifically exon 20 insYVMA (Y772 A775dup), insGSP (G778 P780dup), insTGT (G776delinsVC), single base pair substitutions L 755A, L755S, V777L, V659E S310F, or another HER2 mutation approved by the principal investigator
  • For cohorts 2, 3, 4, documented HER2 amplification identified through next generation sequencing by Memorial Sloan-Kettering Cancer Center (MSK)-Integrated Mutation Profiling for Actionable Cancer Targets (IMPACT) or at another Clinical Laboratory Improvement Amendments (CLIA) laboratory, or documented HER2 amplification by in-situ hybridization (ISH) with HER2/ centromeric probe for chromosome 17 (CEP17) ratio >= 2.0 at a CLIA laboratory; patients with HER2 amplification identified by another method or criteria must be approved by the principal investigator and may enroll in the “other” cohort 4
  • Measurable or evaluable indicator lesion(s) as defined by RECIST v1.1; patients without RECIST measurable disease will be eligible for enrollment to "Other" cohort provided their disease can be evaluated using another accepted response criteria (e.g. Gynecologic Cancer InterGroup [GCIG] CA125 response criteria, positron emission tomography [PET] Response Criteria in Solid Tumors [PERCIST])
  • Karnofsky performance status 70% or above
  • Left ventricular ejection fraction (LVEF) >= 50% measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
  • Negative beta-human chorionic gonadotropin (hCG) pregnancy test within 2 weeks before enrollment for premenopausal women of reproductive capacity and for women less than 12 months after menopause; pregnancy screening will be conducted for women up to the age of 50 years per institutional standard
  • Women of child bearing potential must agree to use of a highly effective method of contraception from the time of informed consent until 6 months after the last dose of ado-trastuzumab emtansine; men must agree to use a barrier method of contraception while on treatment and for 6 months after the last dose of ado-trastuzumab emtansine
  • Absolute neutrophil count >= 1,000/uL within 30 days prior to course 1 day 1 (C1D1)
  • Platelet count >= 100,000/uL within 30 days prior to C1D1
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), in case of Gilbert's syndrome, =< 2 x ULN within 30 days prior to C1D1
  • Aspartate aminotransferase and/or alanine aminotransferase =< 3 x ULN (=< 5 x ULN if liver metastases are present) within 30 days prior to C1D1
  • Provide written, informed consent to participate in the study and follow the study procedures

Exclusion Criteria

  • Prior therapy resulting in cumulative epirubicin dose >= 900 mg/m^2 or cumulative doxorubicin dose >= 500mg/m^2 or equivalent dose of another anthracycline
  • Prior therapy with ado-trastuzumab emtansine (patients who had prior trastuzumab or other HER2 targeted agents are eligible)
  • Symptomatic congestive heart failure (New York Heart Association classification Il-IV)
  • Myocardial infarction or unstable angina within 6 months of enrollment
  • Unstable ventricular arrhythmia requiring treatment
  • Grade 3 or worse peripheral neuropathy as defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.1
  • Women who are pregnant or breast-feeding
  • Known hypersensitivity to any component of ado-trastuzumab emtansine

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Bob T. Li
Phone: 646-888-4201


I. To evaluate the objective response rate (complete plus partial response rate) of trastuzumab emtansine (ado-trastuzumab emtansine) in each primary-site-defined cohort of patients with HER2 amplified solid tumors, and HER2 mutant lung cancers according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.


I. To evaluate progression-free survival (PFS) in each cohort.

II. To evaluate the duration of response (DOR) in each cohort.

III. To evaluate overall survival (OS) in each cohort.

IV. To evaluate side effects of ado-trastuzumab emtansine in patients with HER2 amplified or HER2 overexpressed cancers, or HER2 mutant lung cancers.


I. To explore the molecular associations between the HER2 biomarkers: gene amplification (by next generation sequencing [NGS] and in situ hybridization [ISH]), protein overexpression by immunohistochemistry (IHC) and gene mutations in each cohort.

II. To examine objective response rate (ORR) in each cohort by different types of molecular alterations, HER2 amplification (by NGS and ISH separately), mutation and HER2 overexpression, and assess their predictive value for response.

III. To evaluate the predictive value of changes in circulating tumor deoxyribonucleic acid (DNA) variant allele frequency during treatment for response to ado-trastuzumab emtansine.

IV. Demonstrate the predictive value of pre-treatment tumor uptake of zirconium Zr 89 (89Zr)-trastuzumab and the degree of heterogeneity of uptake for the treatment response to T-DM1.


Patients receive trastuzumab emtansine intravenously (IV) over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 weeks, at 12 weeks, and then every 12 weeks thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Bob T. Li

  • Primary ID 15-335
  • Secondary IDs NCI-2016-00262
  • ID NCT02675829