19 December 2022 07:10 GMT
Imfinzi plus Imjudo recommended for approval in the EU
by CHMP for the treatment of advanced liver and lung cancers
Positive opinions based on significant survival benefit
in HIMALAYA and POSEIDON Phase III trials
AstraZeneca’s Imfinzi (durvalumab) and Imjudo (tremelimumab) combinations have been recommended for marketing authorisation in the European Union (EU) for advanced liver and lung cancers.
The concurrent positive opinions recommend authorising Imfinzi in combination with Imjudofor 1st-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC); andImfinzi in combination with Imjudoand platinum-based chemotherapy for the treatment of adult patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinions on results from theHIMALAYAPhase III trial, which was published intheNew England Journal of Medicine Evidence, and results from thePOSEIDON Phase III trial, which was published in theJournal of Clinical Oncology.
Bruno Sangro, MD, PhD, Director of the Liver Unit at Clínica Universidad de Navarra, Professor of Internal Medicine at the University of Navarra School of Medicine and a lead investigator in the HIMALAYA trial, said: “Liver cancer is a leading cause of cancer death in Europe, and patients with advanced disease face an especially grim prognosis with limited treatment options in the 1st-line setting. The combination of Imjudo and Imfinzi demonstrated a meaningful improvement in overall survival with no increase in severe liver toxicity or bleeding risk, which are important considerations for these patients who often have advanced disease.”
Solange Peters, MD, PhD, President of the European Society for Medical Oncology (ESMO), head of the medical oncology service and chair of thoracic oncology at Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and principal investigator in the POSEIDON trial, said: “Metastatic non-small cell lung cancer remains a complex and devastating diagnosis and there is still an urgent need for new life-extending treatment options. The latest data from the POSEIDON trial demonstrate the long-term survival benefit of Imjudo added to Imfinzi and chemotherapy and support the important role this novel combination could have for patients with metastatic non-small cell lung cancer in Europe.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Patients in Europe diagnosed with these advanced cancers urgently need treatment combinations that can help them live longer. If approved, these Imjudo and Imfinzi combinations will provide patients with novel options that harness the potential long-term survival benefits seen with CTLA-4 inhibition.”
Imjudo and Imfinzi in liver cancer
The CHMP positive opinion for the treatment of HCC is based on results from the HIMALAYA Phase III trial, in which a single dose of the anti-CTLA-4 antibody Imjudo 300mg added to the anti-PD-L1 antibody Imfinzi 1500mg followed by Imfinzi every four weeks (STRIDE regimen) reduced the risk of death by 22% versus sorafenib (hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.66-0.92; p= 0.0035). An estimated 31% of patients treated with the combination were still alive after three years, with 20% of patients treated with sorafenib still alive at the same duration of follow-up.
The safety profiles of the combination of Imjudo added to Imfinzi and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified.
Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.1,2 Approximately 87,000 Europeans were diagnosed with liver cancer in 2020, with 51% of patients at an advanced cancer stage at time of diagnosis. Rates of liver cancer continue to rise rapidly, with a 70% increase of liver cancer-related mortality in the EU from 1990-2019.3
Imjudo and Imfinzi in lung cancer
The CHMP positive opinion for the treatment of metastatic NSCLC is based on results from the POSEIDON Phase III trial, which showed patients treated with a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy experienced a 23% reduction in the risk of death versus a range of chemotherapy options (HR 0.77; 95% CI, 0.65-0.92; p=0.00304). An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI, 0.60-0.86; p=0.00031).
Updated results from the POSEIDON Phase III trial after approximately four years of follow-up presented at the European Society for Medical Oncology Congress 2022 demonstrated sustained survival benefit, improving overall survival (OS) by 25% compared to chemotherapy alone (HR 0.75; 95% CI, 0.63-0.88). An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone.
The safety profile for Imjudo plus Imfinzi and chemotherapy was consistent with the known profiles of each medicine, and no new safety signals were identified.
Stage IV is the most advanced form of lung cancer and is often referred to as metastatic disease.4,5 Approximately 40% of people with NSCLC have Stage IV disease at the time of diagnosis.6 Almost 5% of patients with metastatic NSCLC in England will survive five years after diagnosis, based on data between 2013-2017.7
In October 2022, Imjudo plus Imfinzi was approved in the US for the treatment of adults with unresectable HCC. Imjudo plus Imfinzi in combination with platinum-based chemotherapy was approved in the US in November 2022 for the treatment of adults with metastatic NSCLC. Regulatory applications for both indications are also currently under review in several other countries based on the HIMALAYA and POSEIDON results, respectively.