Date: 2016-10-10
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2016 Congress
Company: AstraZeneca (UK)
Product: durvalumab (MEDI4736) and ISIS-STAT3Rx (AZD9150) or AZD5069
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor/antisense oligonucleotide/CXCR2 antagonist. Durvalumab (MEDI4736) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics. This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells. ISIS-STAT3 Rx (AZD9150) is an antisense drug discovered by Isis and being developed to treat patients with cancers with a strong link to STAT3, such as hepatocellular carcinoma. ISIS-STAT3 Rx, also referred to as AZD9150, is designed to specifically reduce the production of signal transducer and activator of transcription 3 (STAT3). STAT3 is a gene that blocks natural cell death and is critical for tumor cell growth and survival. Inhibition of STAT3 has been shown to block the induction of tumor-associated cytokines involved in the progression of cancer, such as IL-6, IL-1, TGFb, and IL-10, which could serve as important biomarkers in clinical studies. AZD5069 is a CXCR2 antagonist of the human CXCR2 receptor.
Disease: metastatic squamous cell carcinoma of the head and neck
Therapeutic area: Cancer - Oncology
Country: Belgium, Canada, Germany, Italy, Spain, UK, USA
Trial
details: This multicentre, open-label, Phase 1b/2 study is designed as a 2 part study consisting of a dose-escalation Part A and a dose-expansion Part B. The study will assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of MEDI4736 in combination with AZD9150 or AZD5069 in patients with advanced solid malignancies and subsequently comparing AZD9150 and AZD5069 both as monotherapy and in combination with MEDI4736 as second line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. (NCT02499328)
Latest
news: * On October 10, 2016, AstraZeneca and its global biologics research and development arm, MedImmune, announced that early results from the Phase Ib/IIa trial (SCORES) assessing the safety and activity of durvalumab combined with the novel small-molecule STAT3 inhibitor AZD9150 or CXCR2 antagonist AZD5069 in patients with advanced cancers also showed encouraging anti-tumour activity for the two new potential medicines in combination. Among patients receiving durvalumab plus AZD9150 (n=11), two patients achieved a partial response, and five patients demonstrated stable disease. Among patients receiving AZD5069 (n=20), one patient demonstrated complete response, two patients demonstrated partial response, and five patients demonstrated stable disease.4 Both arms determined the recommended dose for Phase II trials.4 The most common AEs were thrombocytopenia (64%), ALT/AST increase (46%), nausea (36%) and neutropenia (36%) among patients receiving AZD9150, and neutropenia (35%), fatigue (25%), and anaemia, anorexia, nausea or pain (all 15%) among patients receiving AZD5069.4 One Grade 3 dose-limiting toxicity occurred at the 40 mg/kg dose of AZD5069, and two similar toxicities were noted at 80 mg/kg.
