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01-11-2019 | Lapatinib | Clinical Trial Report

A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies

Authors: Filipa Lynce, Hongkun Wang, Emanuel F. Petricoin, Paula R. Pohlmann, Brandon Smaglo, Jimmy Hwang, Aiwu R. He, Deepa S. Subramaniam, John Deeken, John Marshall, Michael J. Pishvaian

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2019

Abstract

Purpose

This phase I trial evaluated the maximum tolerated dose, safety and preliminary efficacy of lapatinib, a HER1, HER2 dual kinase inhibitor plus bortezomib, a proteasome inhibitor, in adult patients with advanced malignancies.

Methods

Patients were enrolled in a standard 3 + 3 design with lapatinib (L) 750, 1000, 1250 or 1500 mg daily, and bortezomib (B) 0.7, 1.0, 1.3 or 1.6 mg/m² for 3 weeks with 1 week off. Dose-limiting toxicities (DLT) were assessed during the first 28 days

Results

Fifteen patients received the combination of lapatinib and bortezomib in three different cohorts and ten were evaluable for DLT. There were no DLTs. Anorexia was the most common adverse event. Biomarker analysis showed upregulation of p27 expression with lapatinib and the combination. No tumor response was observed and thus the study was closed early.

Conclusion

The combination of lapatinib and bortezomib was well tolerated but no complete or partial tumor responses were observed at the dose levels tested.

ClinicalTrials.gov Identifier

NCT01497626.

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Title: A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies
Authors: Filipa Lynce
Hongkun Wang
Emanuel F. Petricoin
Paula R. Pohlmann
Brandon Smaglo
Jimmy Hwang
Aiwu R. He
Deepa S. Subramaniam
John Deeken
John Marshall
Michael J. Pishvaian
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keyword: Lapatinib
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03947-7

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Abstract

Purpose

Methods

Results

Conclusion

ClinicalTrials.gov Identifier

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