Original research
A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced or metastatic squamous non-small cell lung cancer

https://doi.org/10.1136/esmoopen-2019-000532Get rights and content
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ABSTRACT

Purpose

This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity.

Patients and methods

This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m2) administered intravenously on a every 3-week schedule. Adverse event (AE) rates and tumour responses were determined. Heregulin messenger RNA (mRNA) and HER3 protein expression were investigated in archival tumour biopsies.

Results

Altogether, 12 patients received lumretuzumab in combination with carboplatin and paclitaxel. The most frequent AEs were gastrointestinal, haematological and nervous system toxicities, which were generally mild and manageable. Partial responses were observed in 3 of 12 patients lasting 81, 177 and 207 days. All responses were achieved in tumours expressing higher heregulin mRNA levels.

Conclusion

Lumretuzumab in combination with carboplatin and paclitaxel was well tolerated. Objective responses were enriched in tumours expressing higher heregulin mRNA levels.

human epidermal growth factor receptor 3 (HER3)
ErbB3
phase i
heregulin
non-small cell lung cancer (NSCLC)
squamous
biomarker

Cited by (0)

J-MC and WJ contributed equally.

Previous presentation of data: Annals of Oncology, Volume 27, Issue suppl_6, 1 October 2016, 372P.

Contributors: All authors contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript.

Funding: This study was funded by F. Hoffmann–La Roche Ltd.

Competing interests: WJ, MC, MH and MW are the sponsor employees and have sponsor stock ownership. CA and FM are also the sponsor employees. IJ is the sponsor consultant from A4P. AC is the member of the Speaker Bureau of Roche and got research support from Roche.

Patient consent for publication: Not required.

Ethics approval: Local ethics committee approval was obtained.

Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement: Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.