Advanced HER2-positive Breast Cancer or Gastric Cancer
Conditions
Keywords
Advanced HER2-positive Breast cancer or Gastric cancer
Brief 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.
Interventions
DRUGLJM716
LJM716
DRUGTrastuzumab
Trastuzumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence rate of Dose Limiting Toxicities | 4 weeks | Incidence of dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of serious adverse events | 4 months | Safety assessment |
| Pharmacodynamic response to LJM716 in tumor tissue | 3 months | Post-treatment change from baseline in pHER3 levels in the tumor |
| Progression-free survival | 18 months | Efficacy assessment |
| Duration of response | 18 months | Efficacy assessment |
| Number of adverse events | 4 months | Safety assessment |
| Serum concentration of LJM716 when administered in combination with trastuzumab | 4 months | PK profile |
| Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST) | every 2 months up to 18 months | Efficacy assessment |
| Frequency of complete responses according to RECIST | every 2 months up to 18 months | Efficacy assessment |
| Frequency of stable disease according to RECIST | every 2 months up to 18 months | Efficacy assessment |
| Serum concentration of anti-LJM716 antibodies | 4 months | Incidence of antibodies against LJM716 |
Countries
Belgium, France, Italy, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed