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
Enriqueta Felip,
Juan-Miguel Cejalvo,
Wolfgang Jacob,
Tania Fleitas Kanonnikoff,
Alejandro Navarro Mendivil,
Maria Martinez Garcia,
Alvaro Taus Garcia,
Natasha Leighl,
Ulrik Lassen,
Morten Mau-Soerensen,
Celine Adessi,
Francesca Michielin,
Ian James,
Maurizio Ceppi,
Max Hasmann,
Martin Weisser
Affiliations
Enriqueta Felip
3Vall d’ Hebron Institute of Oncology, Barcelona, Spain
Juan-Miguel Cejalvo
Department of Medical Oncology, Biomedical Research Institute INCLIVA, CiberOn, University of Valencia, Valencia, Spain
Wolfgang Jacob
Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany
Tania Fleitas Kanonnikoff
Department of Medical Oncology, Institute of Health Research INCLIVA, University of Valencia, Valencia and CIBERONC, Institute of Health Carlos III, Madrid, Spain
Alejandro Navarro Mendivil
Department of Medical Oncology, University Hospital Vall d'Hebron, Barcelona, Spain
Maria Martinez Garcia
Department of Medical Oncology, Hospital del Mar, Barcelona, Spain
Alvaro Taus Garcia
Department of Medical Oncology, Hospital del Mar, Barcelona, Spain
Natasha Leighl
Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Ulrik Lassen
Department of Oncology, Rigshospitalet, Copenhagen, Denmark
Morten Mau-Soerensen
Department of Oncology, Rigshospitalet, Copenhagen, Denmark
Celine Adessi
Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland
Francesca Michielin
Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland
Ian James
A4PConsulting Ltd, Sandwich, United Kingdom
Maurizio Ceppi
Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland
Max Hasmann
Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany
Martin Weisser
Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany
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.
