Date: 2014-11-20
Type of information: Presentation of results at a congress
phase: 1b-2a
Announcement: presentation of results at the 26th European Organization for Research and Treatment of Cancer(EORTC) – the National Cancer Institute (NCI) – and the American Association for Cancer Research (AACR) symposium
Company: Isis Pharmaceuticals (USA), now Ionis Pharmaceuticals (USA) AstraZeneca (UK)
Product: ISIS-STAT3Rx (AZD9150)
Action
mechanism: antisense drug. ISIS-STAT3 Rx 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.
Disease: advanced metastatic hepatocellular carcinoma
Therapeutic area: Cancer - Oncology
Country: Hong Kong, Japan, Republic of Korea, Taiwan
Trial
details: The Phase 1b/2a study will evaluate the safety and efficacy of ISIS-STAT3 Rx in patients with hepatocellular carcinoma who have failed first-line therapy. The endpoints for the study include measurements of anti-tumor activity, STAT3 protein levels in tumor biopsies and STAT3-related biomarkers. The study will also evaluate safety. (NCT01839604)
Latest
news: * On November 20, 2014, Isis Pharmaceuticals announced that data from ISIS-STAT3Rx (AZD9150) will be presented by researchers at AstraZeneca in three presentations at the 26th European Organization for Research and Treatment of Cancer(EORTC) – the National Cancer Institute (NCI) – and the American Association for Cancer Research (AACR) symposium. Results from a Phase 1/2 clinical study presented provided preliminary evidence of antitumor activity for ISIS-STAT3Rx (AZD9150) in patients with cancer including advanced/metastatic hepatocellular carcinoma (HCC). This adds to previous data for ISIS-STAT3Rx showing evidence of antitumor activity in other cancer types, including diffuse large B cell lymphoma. Additional data to be presented at the conference demonstrate that ISIS-STAT3Rx reduced STAT3 levels in multiple cell types relevant to cancer growth and survival, clinically and pre-clinically. Clinical data from ISIS-STAT3Rx were presented in an oral presentation titled, 'Results of a Phase 1, open-label, muticentre study to assess the safety, tolerability, pharmacokinetics and preliminary antitumor activity of AZD9150 in patients with advanced/metastatic hepatocellular carcinoma' on Thursday, Nov. 20. In this presentation, treatment with ISIS-STAT3Rx provided evidence of antitumor activity in patients with HCC. In this late-stage population, several patients experienced stable disease and one patient experienced a durable, partial response (78% tumor shrinkage) while on ISIS-STAT3Rx treatment. Preclinical data from ISIS-STAT3Rx have been presented in a poster titled, 'Immunological STAT3 knockdown associated with antitumor activity in preclinical models translates to clinical samples, suggesting immune modulation contributes to the clinical activity of AZD9150, a therapeutic STAT3 ASO'. Preclinical and clinical data from this presentation show that ISIS-STAT3Rx is distributed to tumor, stromal and immune cells and are consistent with reduction of STAT3 in these cells contributing to antitumor activity. Based on these findings, as well as very encouraging preclinical data in animal models of cancer, AstraZeneca plans to evaluate ISIS-STAT3Rx as an immunomodulatory agent in combination with MEDI4736, AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor. Clinical studies are expected to initiate in the first half of 2015. Isis Pharmaceuticals and AstraZeneca entered into a collaboration, development and license agreement in 2012 in oncology, subsequently expanded in 2013 to include CVMD. Under the 2012 agreement, one of the molecules being developed is ISIS-STAT3Rx, a first-in-human, first-in-class, generation 2.5 antisense oligonucleotide inhibitor of STAT3, which is being developed as an immunomodulatory agent in combination with MEDI4736, AstraZeneca'sinvestigational anti-PD-L1 immune checkpoint inhibitor. A second product of that collaboration, a generation 2.5 antisense drug targeting the androgen receptor, ISIS-ARRx, is in a Phase 1/2 study. This month, Isis and AstraZenecaexpanded their relationship by entering into a collaboration to develop novel delivery methods for antisense oligonucleotides. This new collaboration builds on the existing relationship and could also bring benefits to these programs. * On May 6, 2013, Isis Pharmaceuticals has announced the initiation of a Phase 1b/2a clinical study of ISIS-STAT3Rx in patients with advanced metastatic hepatocellular carcinoma (HCC). Isis licensed ISIS-STAT3Rx to AstraZeneca as part of a strategic alliance in cancer. AstraZeneca is conducting this newly initiated study in patients with HCC. Isis andAstraZeneca are currently evaluating ISIS-STAT3Rx in two Phase 1b/2a clinical studies in patients with HCC and advanced lymphomas. Because STAT3 is over expressed in numerous types of cancers, ISIS-STAT3Rx has the potential to be broadly useful for both solid and hematological tumors.
