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Clinical Trials

Date: 2018-09-25

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the IASLC 19th World Conference on Lung Cancer

Company: AstraZeneca (UK)

Product: Imfinzi® (durvalumab) (MEDI4736)

Action mechanism:

  • monoclonal antibody/immune checkpoint inhibitor. 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.
  • AstraZeneca recently received accelerated approval from the US FDA for Imfinzi® in previously treated patients with advanced bladder cancer. Imfinzi is currently approved in the US and Canada for the treatment of patients with unresectable Stage III NSCLC who had not progressed following platinum-based chemoradiation therapy and under regulatory review in the EU, Japan and other jurisdictions with expected decisions in the second half of 2018.

Disease: non-small cell lung cancer (NSCLC)

Therapeutic area: Cancer - Oncology

Country: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hungary, Italy, Japan, Republic of Korea, Mexico, The Netherlands, Peru, Poland, Russian Federation, Singapore, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, UK, Vietnam

Trial details:

  • The PACIFIC clinical trial is a global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non-small cell lung cancer. The trial is being conducted in 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate, and duration of response.(NCT02125461)

Latest news:

  • • On September 25, 2018, AstraZeneca and MedImmune, its global biologics research and development arm, have presented data on overall survival (OS) in the Phase III PACIFIC trial of Imfinzi® during the Presidential Symposium of the IASLC 19th World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Toronto, Canada. Results from the Phase III PACIFIC trial were published simultaneously in the New England Journal of Medicine, showing Imfinzi® significantly improved OS, the second primary endpoint of the trial, compared to standard of care regardless of PD-L1 expression, reducing the risk of death by 32% (HR 0.68, 99.73% CI 0.47-0.997; p=0.0025).
    Summary of primary endpoints
      Imfinzi (n=476) Placebo (n=237)
    OS (primary endpoint)1
    Number of deaths (%) 183 (38.4%) 116 (48.9%)
    Hazard ratio (99.73% CI)2,3 0.68 (0.47, 0.997)
    p-value2-4 0.0025
    Median in months (95% CI) NR5 (34.7, NR) 28.7 (22.9, NR)
    PFS (primary endpoint)1,6  
    Number (%) of patients with event 243 (51.1%) 173 (73.0%)
    Hazard ratio (95% CI)2,7 0.51 (0.41, 0.63)
    Median in months (95% CI) 17.2 (13.1, 23.9) 5.6 (4.6, 7.7)
    1The data cut-off date for analysis of OS and updated analysis of PFS was 22 March 2018. 2Stratified by sex, age, and smoking history. 3Confidence interval adjusted for interim analysis. 4Criteria for statistical significance at the interim analysis of OS was a p-value ? 0.00274 (using Lan DeMets spending function approximating O’Brien Fleming boundary). 5Not Reached (NR). 6Assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1. 7No formal statistical comparison was made because the study had achieved significance for PFS at the first planned interim analysis (data cutoff of Feb 13, 2017). The safety and tolerability profile for  Imfinzi® was consistent with that reported at the time of the progression-free survival (PFS) analysis. Among patients receiving Imfinzi® the most common adverse reactions (greater than or equal to 20% of patients) versus placebo were cough (35.2% vs. 25.2%), fatigue (24.0% vs. 20.5%), dyspnea (22.3% vs. 23.9%) and radiation pneumonitis (20.2% vs. 15.8%). 30.5% of patients experienced a grade 3 or 4 AE with Imfinzi® vs 26.1% with placebo, and 15.4% of patients discontinued treatment due to AEs with  Imfinzi® vs. 9.8% of patients on placebo. • On May 25, 2018, AstraZeneca and MedImmune announced positive overall survival (OS) results for the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi® (durvalumab) in patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease had not progressed following platinum-based chemotherapy concurrent with radiation therapy (CRT).
  • A planned interim analysis conducted by an Independent Data Monitoring Committee concluded that the trial has met its second of two primary endpoints by showing statistically-significant OS benefit with clinically-meaningful improvement in patients receiving Imfinzi® compared to placebo. The safety and tolerability profile for Imfinzi® was consistent with that reported at the time of the progression-free survival (PFS) analysis. AstraZeneca plans to present results from the PACIFIC trial at a forthcoming medical meeting. In May 2017, AstraZeneca announced that the PACIFIC trial met its first primary endpoint of PFS by demonstrating a median improvement of 11.2 months vs. placebo, as assessed by blinded independent central review.
  • • On September 8, 2017, AstraZeneca and MedImmune, its global biologics research and development arm, have presented the full PFS data from a planned interim analysis of the Phase III PACIFIC trial. Results show that Imfinzi® (durvalumab) demonstrated a statistically-significant and clinically-meaningful improvement in PFS compared to current standard of care with active surveillance in patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy (CRT).
  • Results of the Phase III PACIFIC trial, included at the Presidential Symposium I of the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, show an improvement in PFS of more than 11 months in patients treated with Imfinzi® compared to placebo (full details in table below). The PFS improvement with Imfinzi® was observed across all pre-specified subgroups, including PD-L1 expression status. Patients receiving Imfinzi also had a lower incidence of metastases than those receiving placebo. The PACIFIC trial continues to evaluate overall survival (OS), the other primary endpoint. Detailed results of the PACIFIC trial are published online in the New England Journal of Medicine.
  • • On May 12, 2017, AstraZeneca announced positive results for the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi® (durvalumab) as sequential treatment in patients with locally-advanced, unresectable (Stage III) non-small cell lung cancer (NSCLC) who had not progressed following standard platinum-based chemotherapy concurrent with radiation therap
  • A planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC) concluded that the trial has already met a primary endpoint by showing statistically-significant and clinically-meaningful PFS, as assessed by blinded independent central review, in patients receiving Imfinzi compared to placebo. The results also demonstrate a favourable benefit/risk profile. The trial will also evaluate overall survival (OS), the other primary endpoint, which will be assessed in due course as specified by the protocol. AstraZeneca plans to submit the initial results from the PACIFIC trial for presentation at a forthcoming medical meeting.
  • • On May 8, 2014, AstraZeneca announced the start of the Phase III programme for MEDI4736, an immunotherapy in development for the treatment of non-small cell lung cancer (NSCLC) and other cancers. The goal of the PACIFIC trial, the first study in the Phase III NSCLC programme, is to evaluate progression free survival and overall survival of MEDI4736 compared to placebo in patients with locally advanced, unresectable NSCLC (Stage III) following completion of treatment with chemoradiotherapy and no evidence of tumour progression. The PACIFIC trial is the first pivotal study of an immunotherapy in this patient population. A total of 702 patients are anticipated to be randomised into the PACIFIC Phase III study across more than 100 sites globally. The Phase III programme follows the evaluation of clinical activity and the safety profile of MEDI4736 in a Phase I programme. Updated information from early stage studies (monotherapy and early combination data) will be presented at this year’s American Society of Clinical Oncology annual meeting.

Is general: Yes