Background Activation of MET and its ligand hepatocyte growth factor (HGF) are implicated in resistance to epidermal growth factor receptor (EGFR) inhibitors. This Phase I/II trial evaluated rilotumumab (anti-HGF antibody), combined with erlotinib, in patients with metastatic previously treated NSCLC. Methods Phase I adopted a dose de-escalation design with rilotumumab starting at 15 mg/kg intravenously every 3 weeks and erlotinib 150 mg orally daily. Phase II evaluated the disease control rate (RECIST, DCR) of the combination using a Simon 2-stage design. Biomarkers examined included 10 plasma circulating molecules associated with EGFR and MET pathways. Results Without indications for de-escalation, the RP2D was dose level 0. Overall, 45 response-evaluable patients were enrolled (13 squamous, 32 adenocarcinoma; 2 confirmed EGFR mutant, 33 confirmed EGFR wild-type (WT) and 7 KRAS mutant). DCR was 60% (90% CI, 47.1–71.3) in all patients. Median PFS was 2.6 months (90% CI, 1.4–2.7) and median OS was 6.6 months (90% CI, 5.6–8.9). Among EGFR WT patients, DCR was 60.6% (90% CI, 46.3–73.3), median PFS 2.6 months (90% CI, 1.4–2.7) and median OS 7.0 months (90% CI, 5.6–13.4). Elevated baseline levels of neuregulin 1 were associated with longer PFS (HR 0.41, 95% CI 0.19–0.87), while elevated amphiregulin was associated with more rapid progression (HR 2.14, 95% CI 1.48–3.08). Conclusion The combination had an acceptable safety profile and the DCR rate met the pre-specified criteria for success. In the EGFR WT group, DCR rate exceeded published reports for erlotinib alone. High circulating neuregulin 1 may indicate sensitivity to this combination.

The quality of the host immune response in patients with advanced melanoma is compromised with a bias towards Th2-type polarization and a tumor microenvironment that facilitates disease progression. Overcoming tumor-induced immune suppression through strategies that build upon the immunomodulatory qualities and clinical activity of interferon-α as demonstrated in the melanoma adjuvant setting is a major clinical need. The recent advances in the field of immune checkpoint modulation and the unprecedented clinical activity in advanced melanoma opens the door on novel combinations that may overcome tumor tolerogenic mechanisms that are known to suppress the potent anti-tumor impact of interferon-α. Promising preliminary data suggest that such combinations may move the clinical management of advanced melanoma into the next level, beyond what is currently seen with immune checkpoint blockers alone.

The purpose of this article is to demonstrate that corporate governance is essential to the continued functioning of any company, and much attention has been given to its governance processes. In the same way, sustainability is essential to every company's continued functioning and is perhaps the current trendy idea. Whilst it is obvious what corporate governance usually means, the meaning of sustainability is much less clear, and the article revealed how corporate governance and corporate sustainability interact. A cross-sectional design was followed and the data was gathered from 160 company respondents. The findings of the correlation study indicate an important direct corporate governance and corporate sustainability connection among companies. This research may also be used to detect the effects of corporate governance on company sustainability performance and growth. Keywords: Corporate Governance, Corporate Sustainability, Organizational sustainability, Corporate Authority, Governance

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