Phase Ib Trial Trial of Rg7116, a Glycoengineered Monoclonal Antibody Targeting Her3, in Combination with Cetuximab or Erlotinib in Patients with Advanced/Metastatic Tumors of Epithelial Cell Origin Expressing Her3 Protein

ABSTRACT Aim: To evaluate the safety profile of RG7116 in combination with cetuximab or erlotinib. Methods: Patients (pts) with advanced or metastatic carcinomas with centrally confirmed HER3 protein expression were included. RG7116 plus cetuximab (400 mg/m2 followed by 250 mg/m2 qw IV) and RG7116 plus erlotinib (150 mg/day p.o.) combinations were evaluated in a dose escalation study with “3 + 3” design at a starting dose of 400 mg IV of RG7116 in a q2w regimen. Results: Twenty-seven pts were enrolled in 5 cohorts (400 to 2000 mg) in the cetuximab arm. One dose-limiting toxicity (DLT) of grade 3 dehydration was reported in the 800-mg cohort. Twenty-seven pts were enrolled in 4 cohorts (400 …

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.

AbstractPurpose: 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 inv…

First-in-Human Phase I Study of Lumretuzumab, a Glycoengineered Humanized Anti-HER3 Monoclonal Antibody, in Patients with Metastatic or Advanced HER3-Positive Solid Tumors

Abstract Purpose: A first-in-human phase I study was conducted to characterize safety, efficacy, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of lumretuzumab, a humanized and glycoengineered anti-HER3 monoclonal antibody, in patients with advanced cancer. Experimental Design: Twenty-five patients with histologically confirmed HER3-expressing tumors received lumretuzumab (100, 200, 400, 800, 1,600, and 2,000 mg) every two weeks (q2w) in 3+3 dose-escalation phase. In addition, 22 patients were enrolled into an extension cohort at 2,000 mg q2w. Results: There were no dose-limiting toxicities. Common adverse events (any grade) included diarrhea (22 patients, 46.8%), fatigue (21 …

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

Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to lumretuzumab and pertuzumab in ER+ breast cancer.

Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2, HER3, and ERα. We also investigated the additive efficacy of combination regimens consisting of anti-HER3 (lumretuzumab), anti-HER2 (pertuzumab), and endocrine (fulvestrant) therapy in vivo. Our data show that both HER2 and HER3 can directly complex with the ER and can mediate phosphorylation of the …