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

NCT01602406 | Completed Phase 1 FDA Drug

• 2 other identifiers: CLJM716X21022011-004881-13
• Study Type: interventional
• Target: 64
• Locations: 9 countries
• Sites: 11

Brief Summary

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.

Conditions

Advanced HER2-positive Breast Cancer or Gastric Cancer

Keywords

Advanced HER2-positive Breast cancer or Gastric cancer

Outcome Measures

Primary Outcomes (1)

• Incidence rate of Dose Limiting Toxicities

  Incidence of dose-limiting toxicities (DLTs)

  4 weeks

Secondary Outcomes (10)

• Number of adverse events

  4 months

• Number of serious adverse events

  4 months

• Pharmacodynamic response to LJM716 in tumor tissue

  3 months

• Progression-free survival

  18 months

• Duration of response

  18 months

Study Arms (1)

LJM716 in combination with trastuzumab

EXPERIMENTAL

Drug: LJM716; Drug: Trastuzumab

Interventions

LJM716 DRUG

LJM716

LJM716 in combination with trastuzumab

Trastuzumab DRUG

Trastuzumab

LJM716 in combination with trastuzumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27514, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19111, United States

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Saint-Herblain, 44805, France

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Oxford, OX3 7LJ, United Kingdom

Location

Related Links

• Results for CLJM716X2102 from the Novartis Clinical Trials Website

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

elgemtumab; Trastuzumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 21, 2012
• Study Start: September 21, 2012
• Primary Completion: August 2, 2017
• Study Completion: August 2, 2017
• Last Updated: December 19, 2020

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1); NL (1); IT (1); GB (1); ES (1); BE (1); US (3); FR (1); KR (1)