AstraZeneca’s immunotherapies Imfinzi (durvalumab) and Imjudo (tremelimumab) have been approved in Japan for the treatment of three cancer types: advanced liver, biliary tract and lung.
The approvals authorise Imfinzi in combination with Imjudo for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC) and for the treatment of adult patients with unresectable, advanced or recurrent non-small cell lung cancer (NSCLC) in combination with chemotherapy. Imfinzi was also authorised for the treatment of adult patients with unresectable HCC as monotherapy and for the treatment of adult patients with curatively unresectable biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).
The concurrent approvals by the Japanese Ministry of Health, Labour, and Welfare are based on positive results from the HIMALAYA and TOPAZ-1 Phase III trials, each published in the New England Journal of Medicine Evidence and the POSEIDON Phase III trial, published in the Journal of Clinical Oncology.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Japan has one of the highest rates of diagnosis for liver and biliary tract cancers in the world, and lung cancer remains the country’s leading cause of cancer death. With these approvals for Imfinzi and Imjudo, patients in Japan can now be treated with novel immunotherapy-based treatment regimens that have demonstrated significant survival benefits across three complex cancers with poor prognoses.”
Imfinzi and Imjudo approved in liver cancer
The approval of Imfinzi in combination with Imjudo for the treatment of unresectable HCC brings the first dual immunotherapy treatment regimen to patients in Japan. The approval 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: Single Tremelimumab Regular Interval Durvalumab) significantly reduced the risk of death versus sorafenib. The addition of Imjudo to Imfinzi did not increase severe liver toxicity, and no bleeding risk was observed.
HIMALAYA also served as the basis for the approval of Imfinzi monotherapy in the same disease setting. In HIMALAYA, Imfinzi demonstrated non-inferior overall survival (OS) compared to sorafenib, and an improved tolerability profile versus sorafenib.
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 fifth-leading cause of cancer death in Japan and the sixth most commonly diagnosed cancer worldwide.1,2 HCC is the most common type of liver cancer with 80% of cases occurring in the Asia-Pacific region. In Japan, approximately 45,000 people are diagnosed with HCC and 32,000 die of the disease each year.
Imfinzi and Imjudo approved in NSCLC
The approval of Imfinzi and Imjudo plus chemotherapy for the treatment of unresectable, advanced or recurrent NSCLC is based on results from the POSEIDON Phase III trial, which showed a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy significantly reduced the risk of death versus a range of chemotherapy options.
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.
In Japan, lung cancer is the most commonly diagnosed cancer, with more than 138,000 patients diagnosed in 2020. The prognosis for patients with metastatic NSCLC in Japan is particularly poor, as less than 20% will live beyond three years after diagnosis without treatment.
Regulatory applications for Imfinzi and Imjudo are currently under review in the EU and several other countries based on the HIMALAYA, TOPAZ-1 and POSEIDON results.
Imfinzi plus chemotherapy approved in biliary tract cancer
The approval of Imfinzi plus chemotherapy brings the first immunotherapy regimen to patients with curatively unresectable BTC in Japan after more than a decade of limited innovation. The approval is based on results from an interim analysis of the TOPAZ-1 Phase III trial, which showed that Imfinzi plus chemotherapy significantly reduced the risk of death compared to chemotherapy alone. Imfinzi plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.
BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder. In 2021, approximately 23,300 people in Japan were diagnosed with BTC, which is the sixth-leading cause of cancer-related deaths for women and seventh-leading cause of cancer-related death for men in Japan. Patients face a poor prognosis, with approximately 19% to 31% of patients with BTC surviving five years.