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Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: May 7, 2012
Last updated: March 29, 2017
Last verified: March 2017
This is a multicenter, open-label, dose escalation, phase I study to estimate the Maximum Tolerated Dose (MTD) or a lower Recommended Dose for Expansion (RDE) of LJM716 in combination with trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2) overexpressing Metastatic Breast Cancer (MBC) or gastric cancer (MGC). The study consists of a dose escalation part and a dose expansion part. LJM716 will be administered intravenously once weekly unless a less frequent dosing regimen such as every 2 weeks or once every 4 weeks is introduced. Patients will continue on their trastuzumab dosing, administered intravenously once weekly at 2mg/kg. During dose escalation, a minimum of 15 patients are anticipated to be treated in successive cohorts. The dose escalation will continue until the MTD/RDE is declared. The RDE dose selected will either be the MTD or a dose below the MTD based on safety and Pharmacokinetic/Pharmacodynamic (PK/PD) considerations. Following the MTD/RDE declaration, approximately 20 MBC and 20 MGC patients will be enrolled in separate arms in the dose expansion part and treated at the MTD/RDE to further assess the safety, tolerability, and anti-tumor activity of the combination.

Condition Intervention Phase
Advanced HER2-positive Breast Cancer or Gastric Cancer
Drug: LJM716
Drug: Trastuzumab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Dose Escalation, Phase I Study of LJM716 Administered Intravenously in Combination With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast Cancer or Gastric Cancer

Resource links provided by NLM:

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Incidence rate of Dose Limiting Toxicities [ Time Frame: 4 weeks ]
    Incidence of dose-limiting toxicities (DLTs)

Secondary Outcome Measures:
  • Number of adverse events [ Time Frame: 4 months ]
    Safety assessment

  • Number of serious adverse events [ Time Frame: 4 months ]
    Safety assessment

  • Pharmacodynamic response to LJM716 in tumor tissue [ Time Frame: 3 months ]
    Post-treatment change from baseline in pHER3 levels in the tumor

  • Progression-free survival [ Time Frame: 18 months ]
    Efficacy assessment

  • Duration of response [ Time Frame: 18 months ]
    Efficacy assessment

  • Serum concentration of anti-LJM716 antibodies [ Time Frame: 4 months ]
    Incidence of antibodies against LJM716

  • Serum concentration of LJM716 when administered in combination with trastuzumab [ Time Frame: 4 months ]
    PK profile

  • Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: every 2 months up to 18 months ]
    Efficacy assessment

  • Frequency of complete responses according to RECIST [ Time Frame: every 2 months up to 18 months ]
    Efficacy assessment

  • Frequency of stable disease according to RECIST [ Time Frame: every 2 months up to 18 months ]
    Efficacy assessment

Enrollment: 64
Actual Study Start Date: September 21, 2012
Estimated Study Completion Date: December 18, 2017
Estimated Primary Completion Date: December 18, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LJM716 in combination with trastuzumab Drug: LJM716 Drug: Trastuzumab


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with confirmed HER-2 positive, metastatic or non-operable locally advanced breast or gastric cancer
  • Metastatic breast cancer patients must have received a minimum of 1 and a maximum of 3 prior anti HER2 based regimens with documented progression on the most recent regimen which must contain trastuzumab, ado-trastuzumab emtansine or lapatinib
  • Metastatic gastric cancer patients must have received a minimum of 1 and a maximum of 2 prior anti HER2 based regimens with documented progression on the most recent regimen which must contain trastuzumab or ado-trastuzumab emtansine
  • During the dose expansion part of study, all patients must have at least one measurable lesion as defined by RECIST criteria.
  • Patients must have at least one prior trastuzumab-containing regimen
  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2

Exclusion Criteria:

  • Patients with Central Nervous System (CNS) metastasis which are: symptomatic or require treatment for symptom control and/or growing
  • Prior treatment with any anti-HER3 (Human Epidermal growth factor Receptor 3) treatment
  • Impaired cardiac function
  • Prior to the first dose of study treatment, patients who have received systemic antineoplastic therapy or any investigational therapy within 4 weeks or within 5 half- lives of the therapy prior to starting study treatment, whichever is shorter, or for cyclical therapy, within one cycle length (e.g. 6 weeks for nitrosourea, mitomycin-C).
  • Patients who have a history of primary malignancy other than that being treated in this study, and currently requires active clinical intervention.
  • Patients who do not have an archival tumor sample (or sections of it) available or readily obtainable.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
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Please refer to this study by its identifier: NCT01602406

United States, Massachusetts
Massachusetts General Hospital SC-5
Boston, Massachusetts, United States, 02114
United States, North Carolina
University of North Carolina UNC 2
Chapel Hill, North Carolina, United States, 27514
United States, Pennsylvania
Fox Chase Cancer Center FCC 2
Philadelphia, Pennsylvania, United States, 19111-2497
Novartis Investigative Site
Wilrijk, Belgium, 2610
Novartis Investigative Site
Saint Herblain cedex, France, 44805
Novartis Investigative Site
Milano, MI, Italy, 20133
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03080
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46010
Novartis Investigative Site
Taipei, Taiwan, 10002
United Kingdom
Novartis Investigative Site
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01602406     History of Changes
Other Study ID Numbers: CLJM716X2102
2011-004881-13 ( EudraCT Number )
Study First Received: May 7, 2012
Last Updated: March 29, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Advanced HER2-positive Breast cancer or Gastric cancer

Additional relevant MeSH terms:
Breast Neoplasms
Stomach Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents processed this record on May 25, 2017