EGFR overexpression + HER-2 overexpression

The Herceptin-resistant breast cancer cell line JIMT-1 was used in an in vivo tumor model, and MMTV-erbB2 (Fo5) transgenic mice models were used to evaluate the efficacy and safety of ER121 as neoadjuvant. ER121 is a non-toxic small-molecule erbB kinase inhibitor and holds promise as an oral and systemic therapeutic agent for treating progressive erbB-driven tumors in therapeutic settings. Moreover, ER121 shows potential as a preventive therapy in neoadjuvant settings for erbB2-associated tumors and when administered systemically can dramatically limit erbB2 brain metastases in animal models.

No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

The frequencies of MSI and HER-2 over-expression were 21.8% (71/ 326), and 12.6% (41/ 326), respectively. The frequency of EGFR over-expression was 45.4% (148/ 326). In microsatellite stable (MSS) GCs, the over-expression of HER-2 and EGFR of AGCs was more frequent than EGCs (P< 0.01) (P= 0.03).

Conclusions Varlitinib combined with paclitaxel revealed manageable toxicities and antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy. Updated outcomes for ongoing patients and biomarker analysis will be presented.

Using the assay, the expression level of EGFR-HER2 dimer and its relationship with individual protein monomers were determined in four breast cancer cell lines. We are among the first to obtain the absolute level of protein heterodimer, and this quantitative information may be vital in understanding the molecular basis of cancer.

Our results suggest that HECrossMAb may function as a potential therapeutic agent for the treatment of NSCLC overexpressing EGFR and HER2.

Moreover, after crossing the endothelial monolayer, HFn-conjugated mAbs retain their biological activity against targets, as assessed by MTS and ADCC assays. Our data support the use of HFn as efficient carrier to enhance the BBB crossing of mAbs, without affecting their antitumoral activity.

Background: EGFR and HER2 are over-expressed in gastric cancer, and activation of EGFR signaling in HER2-overexpressing gastric cancer can confer resistance to HER2-directed treatment like trastuzumab. The combination of varlitinib 300mg bid and weekly paclitaxel 80mg showed manageable safety profiles and determined as RP2D. Currently, multi-site phase 2 part is now underway.