Date: 2015-05-14
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
Company: AstraZeneca (UK)
Product: Tagrisso® -AZD9291 (osimertinib) and durvalumab (MEDI4736)
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor/kinase inhibitor/tyrosine kinase 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. AZD9291/Osimertinib is an irreversible inhibitor of epidermal growth factor receptors that harbour sensitising mutations (EGFRm) and TKI-resistance mutation T790M. Nearly two out of three patients with NSCLC whose disease progresses after treatment with an EGFR inhibitor develop the T790M mutation, for which treatment options are limited. A small number of patients (approximately 3-5%) have the T790M mutation at NSCLC diagnosis.
Disease: locally advanced or metastatic EGFR T790M+ non small cell lung cancer
Therapeutic area: Cancer - Oncology
Country: Canada, Republic of Korea, Switzerland, Taiwan, Australia, Belgium, Germany, Hong Kong, Italy, Japan, Spain, UK, USA
Trial
details: The CAURAL study is a phase III, multi centre, open label, randomized, study to assess the efficacy and safety of AZD9291 (80 mg, orally, once daily) in combination with MEDI4736 (10 mg/kg (IV) infusion q2w) versus AZD9291 monotherapy (80 mg, orally, once daily) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) T790M mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. The randomization will be stratified by previous lines of treatment (2nd or 3rd+) and ethnicity (Asian or Non-Asian). A mandatory biopsy will be needed for central testing of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 in combination with MEDI4736 versus AZD9291 monotherapy by assessment of Progression Free Survival (PFS) by investigators according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Approximately 350 patients will be evaluated and will consist of 2 populations: 2nd line (patients who have progressed following an approved first-line EGFR-TKI treatment but who have not received further treatment) and 3rd line or higher (patients who have progressed following prior therapy with an approved EGFR-TKI and an additional anti-cancer treatment. Patients may have also received additional lines of treatment). (NCT02454933)
Latest
news: * On May 14, 2015, a Phase 3 trial sponsored by AstraZeneca was published on the NIH website ClinicalTrials.gov for durvalumab (MEDI4736) and is currently recruiting participants.
