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Poster display

1558 - Impact of tumor heregulin mRNA expression on outcome of patients with advanced/metastatic squamous NSCLC treated with lumretuzumab, a glycoengineered monoclonal antibody targeting HER3, in combination with erlotinib

Date

10 Oct 2016

Session

Poster display

Presenters

Didier Meulendijks

Citation

Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368

Authors

D. Meulendijks1, U. Lassen2, A. Cervantes3, J. Han4, A. Calles5, E. Felip6, S. Kim7, J.H.M. Schellens1, A. Taus8, M. Sorensen2, T. Fleitas3, B. Bossenmaier9, F. Michielin10, C. Adessi10, G. Meneses-Lorente11, M. Ceppi9, I. James12, W. Jacob9, M. Weisser9, M. Martinez-Garcia8

Author affiliations

  • 1 Clinical Pharmacology & Medical Oncology, The Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
  • 2 Department Of Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 - Copenhagen/DK
  • 3 Serv. Hematologia Y Oncologia Medica, Institute of Health Research INCLIVA, University of Valencia, 46010 - Valencia/ES
  • 4 Center For Lung Cancer, National Cancer Center, Goyang/KR
  • 5 Centro Integral Oncológico Clara Campal, START-Madrid, Madrid/ES
  • 6 Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 7 Lung Cancer Center, Asan Medical Center, Seoul/KR
  • 8 Department Of Medical Oncology, University Hospital del Mar, Barcelona/ES
  • 9 Roche Innovation Center Munich, Pharma Research and Early Development, 82377 - Penzberg/DE
  • 10 Roche Innovation Center Basel, Pharma Research and Early Development, Basel/CH
  • 11 Roche Innovation Center Welwyn, Pharma Research and Early Development, Welwyn/GB
  • 12 A4p, Consulting Ltd, Sandwich/GB
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Resources

Abstract 1558

Background

Preclinical data suggest that high mRNA expression levels of heregulin (HRG) are associated with anti-tumor activity of HER3-targeted therapy. In addition, studies have shown that HRG mRNA is more highly expressed in squamous (sq)NSCLC compared to non-sq NSCLC. The aim of this study was to evaluate the safety and efficacy of lumretuzumab in combination with erlotinib in sqNSCLC patients and evaluate the impact of tumor HRG mRNA expression levels as potential biomarker.

Methods

Thirty-two patients (pts) with advanced or metastatic sqNSCLC with centrally confirmed tumor HER3 protein expression were studied in a dedicated phase Ib expansion cohort. HRG expression levels were assessed by RT-PCR from pretratment formalin-fixed paraffin-embedded tumor samples. Lumretuzumab (800 mg i.v.) was administered on a q2w regimen in combination with erlotinib (150 mg/day p.o.).

Results

Median age was 66 years, pts had received a median of 2 prior lines of therapy, and 22% had previously received an EGFR inhibitor. In line with a previous report (Lassen et al., Ann Oncol 25; suppl. 4: iv147, 2014), diarrhea (78%) and rash (62%) were the most frequently reported adverse events. Overall, 2 pts (6%) achieved a confirmed PR with a duration of response of 3.8 and 4.9 months, respectively. The overall disease control rate (DCR) was 59% and median PFS was 2.0 months. In tumors expressing higher levels of HRG mRNA (n = 12), defined as expression levels above the median of an in-house sqNSCLC tumor bank (n = 150 samples), ORR and DCR were 8% and 75%, respectively. PFS and duration of response were 2.9 and 3.8 months, respectively. Assessment of alternative cut-off values or assays (IHC or ISH) did not significantly change the efficacy results.

Conclusions

Lumretuzumab in combination with erlotinib demonstrated modest clinical efficacy in sqNSCLC. Higher expression levels of HRG were associated with numerically higher rates of disease stabilization. However, ORR was low and duration of response and stable disease was relatively short, questioning the utility of tumor HRG mRNA as a clinically meaningful and robust biomarker for HER3 targeted therapy in sqNSCLC.

Clinical trial identification

NCT01482377

Legal entity responsible for the study

Roche Pharma Research and Early Development

Funding

Roche Pharma Research and Early Development

Disclosure

U. Lassen: Research funding from Roche.A. Cervantes: Consulting and Advisory role for Roche Speakers bureau for Roche. J-Y. Han: Consulting and Advisory role for BMS, Astra Zeneca, Boehringer Ingelheim Speakers bureau for Astra Zeneca Research funding from BMS, Roche, Astra Zeneca. E. Felip: Consulting and Advisory role for Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene. Honoraria from Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene. Speakers bureau for BMS, Novartis, Roche.M. Sorensen: Travel expenses from Roche. T. Fleitas: Family member employed by MSD. B. Bossenmaier, F. Michielin, C. Adessi: Employee of Roche. G. Meneses-Lorente, M. Ceppi: Employee of Roche and stock ownership. I. James: Employee of Roche and A4P. W. Jacob, M. Weisser: Employee of Roche Stock ownership.All other authors have declared no conflicts of interest.

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