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Figure S1, Figure S2, Figure S3, Figure S4, Figure S5, Figure S6 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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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 Figure 1 Quantile plots of baseline membrane HER3 IRS score (A) and HER3 mRNA log expression (B) in baseline FFPE tumor biopsy samples from patients with known adeno- and squamous cell carcinoma histology Supplementary Figure 2 Quantile plots of baseline membrane HER3 immuno-reactive scores in fresh FFPE tumor biopsies from NSCLC patients with non-squamous or squamous histology Supplementary Figure 3 Quantile plots of baseline HRG mRNA log expression determined by qRT-PCR in FFPE tumor biopsies of adeno- and squamous cell carcinoma histology (data obtained using the HRG research assay) Supplementary Figure 4 Baseline HRG mRNA log expression in FFPE tumor biopsies, determined by qRT-PCR, in non-sqNSCLC and sqNSCLC (data obtained using the HRG prototype diagnostic assay). Dotted line indicates prior determined median HRG expression in sqNSCLC. Supplementary Figure 5 Best percentage change from baseline in sum of longest diameters of target lesions for patients in the dose escalation and extension phase of the cetuximab part (n = 38). Red bars indicate PD patients, blue bars SD patients, light green bars PR patients and dark green bars CR patients. Eleven patients were without target lesion assessment post baseline. Tumor type and lumretuzumab dose are indicated. * indicates patients who received previous EGFR-targeting therapy. a indicates a patient who received prior trastuzumab therapy. Supplementary Figure 6 Best percentage change from baseline in sum of longest diameters of target lesions for patients in the dose escalation phase and the two NRG1 fusion gene patients of the extension phase of the erlotinib part (n = 31). Red bars indicate PD patients, blue bars SD patients and green bars PR patients. Eight patients were without target lesion assessment post baseline. Tumor type and lumretuzumab dose are indicated. * indicates patients who received previous EGFR-targeting therapy. a indicates two patients with NRG1 gene fusion.

History

ARTICLE ABSTRACT

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.