phase i study ljm716 combined with trastuzumab in patients with her2 overexpressing metastatic breast or gastric cancer

Conditions: Advanced HER2-positive Breast Cancer or Gastric Cancer

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.


Eligibility criteria:
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

Keywords: advanced her2-positive breast cancer or gastric cancer