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