Date: 2016-11-22
Type of information: update on patient enrollment
phase: 3
Announcement: update on patient enrollment
Company: AstraZeneca (UK)
Product: durvalumab (MEDI4736) and tremelimumab
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor. 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. Tremelimumab is a fully human monoclonal antibody which binds to the protein CTLA-4, expressed on the surface of activated T lymphocytes.
Disease: squamous cell carcinoma of the head and neck
Therapeutic area: Cancer - Oncology
Country: Austria, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Japan, Republic of Korea, Philippines, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Ukraine, UK, USA, Vietnam
Trial
details: This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or MEDI4736 monotherapy versus SoC (EXTREME regimen) in the treatment of patients with SCCHN who have not received prior systemic chemotherapy for recurrent or metastatic disease. (NCT02551159)
Latest
news: * On November 22, 2016, AstraZeneca announced that the US FDA has lifted the partial clinical hold on the enrolment of new patients with head and neck squamous cell carcinoma (HNSCC) for clinical trials of durvalumab as monotherapy and in combination with tremelimumab or other potential medicines. The Phase III KESTREL trial has already re-opened for new patient enrolment at some clinical study sites and the EAGLE trial is expected to resume recruitment shortly, without amendments to either protocol. AstraZeneca will progressively resume enrolment for all HNSCC trials across the participating sites in the US and globally, subject to national health authority and ethics committee approval where required. The status of active recruitment will be reflected on clinicaltrials.gov in the coming days. The partial clinical hold on new patient enrolment was communicated on 27 October, after preliminary findings from ongoing clinical trials related specifically to head and neck cancer. The FDA lifted the partial clinical hold following a review of the comprehensive analysis provided by AstraZeneca of bleeding events that were observed as part of the routine safety monitoring of the Phase III KESTREL and EAGLE trials. * On October 27, 2016, AstraZeneca confirms that the FDA has placed a partial clinical hold on the enrolment of new patients with head and neck squamous cell carcinoma (HNSCC) in clinical trials of durvalumab as monotherapy and in combination with tremelimumab or other potential medicines. All trials are continuing with existing patients. The partial clinical hold on new patient enrolment relates only to head and neck cancer. Trials for durvalumab in different cancer types, as monotherapy or in combination with tremelimumab or other potential medicines, are progressing as planned, with pivotal data in lung cancer anticipated in the first half of 2017. The FDA’s decision follows voluntary action by AstraZeneca to pause enrolment of new HNSCC patients while a detailed analysis is conducted of adverse events related to bleeding that were observed as part of routine safety monitoring of the Phase III KESTREL and EAGLE trials. Bleeding is a known complication in treatments of head and neck cancers primarily due to the nature of the underlying disease, the proximity of tumours to major blood vessels and use of prior cancer therapies, which may involve surgery and radiation. AstraZeneca has submitted its analysis of the observed bleeding events to the FDA for review and is working closely with the Agency, providing the required information to resume new patient enrolment as soon as possible.
