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

Phase 1

Completed

• Conditions: Advanced HER2-positive Breast Cancer or Gastric Cancer
• Interventions: Drug: LJM716; Drug: Trastuzumab

• Registration Number: NCT01602406
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-05-07
• Study First Submitted QC: 2012-05-18
• Study First Posted: 2012-05-21
• Study Start: 2012-09-21
• Primary Completion: 2017-08-02
• Study Completion: 2017-08-02
• Status Verified: 2018-07
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LJM716 in combination with trastuzumab	Trastuzumab	-
LJM716 in combination with trastuzumab	LJM716	-

Primary Outcome Measures

Name	Time	Method
Incidence rate of Dose Limiting Toxicities	4 weeks	Incidence of dose-limiting toxicities (DLTs)

Secondary Outcome Measures

Name	Time	Method
Serum concentration of LJM716 when administered in combination with trastuzumab	4 months	PK profile
Number of adverse events	4 months	Safety assessment
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
Serum concentration of anti-LJM716 antibodies	4 months	Incidence of antibodies against LJM716
Duration of response	18 months	Efficacy assessment
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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Oxford, United Kingdom