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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced HER2-positive Breast Cancer or Gastric Cancer

Intervention / Treatment
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* Drug: LJM716
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LJM716 in combination with trastuzumab<br> | Drug: LJM716<br>* LJM716<br>Drug: Trastuzumab<br>* Trastuzumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of Dose Limiting Toxicities | Incidence of dose-limiting toxicities (DLTs) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Safety assessment | 4 months | 
| Number of serious adverse events | Safety assessment | 4 months | 
| Pharmacodynamic response to LJM716 in tumor tissue | Post-treatment change from baseline in pHER3 levels in the tumor | 3 months | 
| Progression-free survival | Efficacy assessment | 18 months | 
| Duration of response | Efficacy assessment | 18 months | 
| Serum concentration of anti-LJM716 antibodies | Incidence of antibodies against LJM716 | 4 months | 
| Serum concentration of LJM716 when administered in combination with trastuzumab | PK profile | 4 months | 
| Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST) | Efficacy assessment | every 2 months up to 18 months | 
| Frequency of complete responses according to RECIST | Efficacy assessment | every 2 months up to 18 months | 
| Frequency of stable disease according to RECIST | Efficacy assessment | every 2 months up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced HER2-positive Breast cancer or Gastric cancer