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)

NCT02289833 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: BO293892014-001237-83
• Study Type: interventional
• Target: 49
• Locations: 7 countries
• Sites: 23

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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)

  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.

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

Secondary Outcomes (15)

• Percentage of Participants Who Died

  From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

• Overall Survival (OS)

  From Day 1 to death from any cause, up to the study completion date (approximately 43 months)

• 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)

• 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)

• 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)

Study Arms (2)

Cohort IHC2+

EXPERIMENTAL

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

Cohort IHC3+

EXPERIMENTAL

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

Interventions

Trastuzumab Emtansine DRUG

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.

Also known as: Kadcyla, T-DM1

Cohort IHC2+; Cohort IHC3+

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (23)

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, 32256, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

HELIOS Klinikum Emil von Behring Klinik f.Pneumologie Onkologie u.Infektiologie

Berlin, 14165, Germany

Location

Kaiserswerther Diakonie Florence Nightingale-Krankenh. Tagesklinik f.Onkologie

Düsseldorf, 40489, Germany

Location

Asklepios-Fachkliniken Muenchen-Gauting; Onkologie

Gauting, 82131, Germany

Location

Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II

Halle, 06120, Germany

Location

Fachklinik für Lungenerkrankungen

Immenhausen, 34376, Germany

Location

Azienda Ospedaliera Univ Parma; Dept Oncologia Medica

Parma, Emilia-Romagna, 43100, Italy

Location

Istituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii

Otwock, 05-400, Poland

Location

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

Warsaw, 02-781, Poland

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, 28046, Spain

Location

Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia

Zaragoza, 50009, Spain

Location

CHUV; Departement d'Oncologie

Lausanne, 1011, Switzerland

Location

UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 13, 2014
• Study Start: December 15, 2014
• Primary Completion: October 25, 2016
• Study Completion: August 20, 2018
• Last Updated: August 7, 2019
• Results First Posted: November 22, 2017

Record last verified: 2019-07

Locations

US (5); KR (2); DE (5); ES (4); CH (2); IT (2); PL (3)