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

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

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