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

Novartis

Status and phase

Completed

Phase 1

Conditions

Advanced HER2-positive Breast Cancer or Gastric Cancer

Treatments

Drug: LJM716

Drug: Trastuzumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT01602406

2011-004881-13 (EudraCT Number)

CLJM716X2102

Details and patient eligibility

About

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.

Enrollment

64 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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