American Association for Cancer Research
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Table S1, Table S2 from Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity

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journal contribution
posted on 2023-03-31, 20:30 authored by Didier Meulendijks, Wolfgang Jacob, Emile E. Voest, Morten Mau-Sorensen, Maria Martinez-Garcia, Alvaro Taus, Tania Fleitas, Andres Cervantes, Martijn P. Lolkema, Marlies H.G. Langenberg, Maja J. De Jonge, Stefan Sleijfer, Ji-Youn Han, Antonio Calles, Enriqueta Felip, Sang-We Kim, Jan H.M. Schellens, Sabine Wilson, Marlene Thomas, Maurizio Ceppi, Georgina Meneses-Lorente, Ian James, Suzana Vega-Harring, Rajiv Dua, Maitram Nguyen, Lori Steiner, Celine Adessi, Francesca Michielin, Birgit Bossenmaier, Martin Weisser, Ulrik N. Lassen

Supplementary Table 1 Downregulation of HER3 membrane protein expression in skin biopsies following treatment with lumretuzumab and cetuximab or erlotinib Supplementary Table 2 Change of tumor biomarkers in tumor biopsies following treatment with lumretuzumab and cetuximab or erlotinib



Purpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of HRG mRNA and HER3 mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib.Results: Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor HRG and HER3 mRNA levels were associated with a numerically higher disease control rate but not ORR.Conclusions: The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels. Clin Cancer Res; 23(18); 5406–15. ©2017 AACR.