372P - A phase Ib study of lumretuzumab, a glycoengineered monoclonal antibody targeting HER3, in combination with carboplatin and paclitaxel as 1st-line...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical research
Basic Scientific Principles
Presenter Juan Miguel Cejalvo
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors J.M. Cejalvo1, T. Fleitas2, E. Felip3, A. Navarro Mendivil3, M. Martinez-Garcia4, A. Taus4, N. Leighl5, U. Lassen6, M. Mau Soerensen6, C. Adessi7, F. Michielin7, W. Jacob8, I. James9, M. Ceppi8, M. Weisser8, A. Cervantes10
  • 1Oncology And Hematology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 2Clinical Oncology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 3Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 4Department Of Medical Oncology, University Hospital del Mar, Barcelona/ES
  • 5Medical Oncology, Princess Margaret Hospital, Toronto/CA
  • 6Department Of Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 - Copenhagen/DK
  • 7Roche Innovation Center Basel, Pharma Research and Early Development, Basel/CH
  • 8Roche Innovation Center Munich, Pharma Research and Early Development, 82377 - Penzberg/DE
  • 9Consulting Services, A4P Consulting Ltd, Sandwich/GB
  • 10Medical Oncology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES

Abstract

Background

Preclinical data suggest that high mRNA expression levels of heregulin (HRG) could predict anti-tumor activity of lumretuzumab, an anti-HER3 antibody. HRG mRNA is more highly expressed in squamous (sq)NSCLC compared to non-sqNSCLC.

Methods

This was an open-label, multicenter phase Ib study in patients (pts) with advanced or metastatic sqNSCLC who have not received prior chemotherapy or targeted therapy for NSCLC. Lumretuzumab (800 mg) was administered in combination with carboplatin (AUC 6 mg/mL x min) and paclitaxel (200 mg/m2) on a q3w schedule. The primary objectives were to evaluate safety and efficacy and an exploratory objective was to correlate tumor HRG mRNA expression to clinical activity. HRG mRNA expression levels were assessed by RT-PCR in archival formalin-fixed paraffin-embedded tumor samples. To distinguish high vs low HRG gene expression levels, the median gene expression level of sqNSCLC tumor samples from an internal tumor bank (n = 150) was used as an exploratory cut-off.

Results

Twelve pts were enrolled (median age 66.5 years, 10 pts male). The most frequently reported adverse events (AEs) (in >2 pts) were diarrhea (9 pts), asthenia (8 pts), neurotoxicity (5 pts), nausea and infusion-related reaction (4 pts each). Grade ≥3 AEs were only reported for single pts except for anemia which was reported for two pts. Overall, three pts achieved a partial response (25%) and 8 pts achieved stable disease (67%). High HRG mRNA expression levels were found in 7 pts (58%). All three responding pts showed high HRG mRNA expression levels. The duration of responses were 2.8, 6.0, and 6.2 months.

Conclusions

Lumretuzumab in combination with carboplatin and paclitaxel was safe and well tolerated. While all 3 responding pts had tumors with high HRG mRNA expression levels, the addition of lumretuzumab to platinum-based therapy was not associated with a clear signal of higher clinical activity than what would have been expected with platinum-based therapy alone.

Clinical trial identification

NCT02204345 First received: July 24, 2014

Legal entity responsible for the study

Fa. Hoffmann-La Roche

Funding

Fa. Hoffmann-La Roche

Disclosure

E. Felip: Consulting fees from: Eli Lilly, Pfizer, Roche, Boehringer Ingelheim, MSD Lecture fees from: Astra Zeneca, BMS, Novartis. C. Adessi, F. Michielin, I. James, M. Ceppi, M. Weisser: Sponsor employee. W. Jacob: Sponsor employee Sponsor stock owner. A. Cervantes: Consulting fees from: Merck Serono, Amgen, Servier, Roche, Lilly, Novartis Research support from: Merck Serono, Amgen, Servier, Lilly, Novartis, MSD, Roche, Genentech. All other authors have declared no conflicts of interest.