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

• Number of adverse events [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  Safety assessment
• Number of serious adverse events [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
  Safety assessment
• Pharmacodynamic response to LJM716 in tumor tissue [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  Post-treatment change from baseline in pHER3 levels in the tumor
• Progression-free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  Efficacy assessment
• Duration of response [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  Efficacy assessment
• Serum concentration of anti-LJM716 antibodies [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  Incidence of antibodies against LJM716
• Serum concentration of LJM716 when administered in combination with trastuzumab [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  PK profile
• Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: every 2 months up to 18 months ] [ Designated as safety issue: No ]
  Efficacy assessment
• Frequency of complete responses according to RECIST [ Time Frame: every 2 months up to 18 months ] [ Designated as safety issue: No ]
  Efficacy assessment
• Frequency of stable disease according to RECIST [ Time Frame: every 2 months up to 18 months ] [ Designated as safety issue: No ]
  Efficacy assessment

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.

• Drug: LJM716
• Drug: Trastuzumab

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 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
• 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 (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy within 4 weeks (< 6 weeks for nitrosourea or mitomycin-C, antibodies except for trastuzumab) or within 5-half lives of the investigational therapy prior to starting study treatment, whichever is shorter
• 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