IMFINZI (DURVALUMAB) IN COMBINATION WITH GEMCITABINE AND CISPLATIN APPROVED IN GREAT BRITAIN AS A FIRST-LINE TREATMENT FOR ADULT PATIENTS WITH LOCALLY ADVANCED, UNRESECTABLE OR METASTATIC BILIARY TRACT CANCER

IMFINZI (DURVALUMAB) IN COMBINATION WITH GEMCITABINE AND CISPLATIN APPROVED IN GREAT BRITAIN AS A FIRST-LINE TREATMENT FOR ADULT PATIENTS WITH LOCALLY ADVANCED, UNRESECTABLE OR METASTATIC BILIARY TRACT CANCER

• This authorisation by the MHRA has been issued under Project Orbis, a collaborative, global programme designed to deliver faster patient access to innovative cancer treatments through a framework of concurrent regulatory submission and review.^[1]
• Durvalumab is the first innovation in over ten years in this setting resulting in an Innovation Passport, which is a pre-requisite to participation in Project Orbis and allows entry to the Innovative Licensing and Access Pathway (ILAP). The pathway aims to accelerate patient access to cutting-edge medicines.^[2]
• Results from the TOPAZ-1 Phase III trial showed that durvalumab in combination with gemcitabine and cisplatin more than doubled 2-year overall survival benefit in locally advanced biliary tract cancer versus gemcitabine/cisplatin plus placebo (23.6% versus 11.5%), as well as reducing the risk of death by 24%.^[3]

London, UK, Thursday 2 February 2023 – AstraZeneca today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for Imfinzi (durvalumab) in combination with gemcitabine and cisplatin in Great Britain for use as a first-line treatment of adults with locally advanced, unresectable or metastatic biliary tract cancer (BTC).^[4]

This authorisation by the MHRA has been issued under Project Orbis, an international programme coordinated by the US Food and Drug Administration (FDA), which provides a framework for the concurrent submission and review of oncology medicines among international partners.¹ While the FDA coordinates the programme, each participating country remains completely independent on their final regulatory decision. The MHRA has been a Project Orbis partner since 1 January 2021.¹

Professor John Bridgewater, Clinical Researcher at the University College London (UCL) Cancer Institute, and Medical Oncologist, said: “This decision acknowledges the first improvement in outcomes for patients with advanced biliary tract cancer in first-line treatment in over a decade. Whilst this disease is uncommon, the incidence is rising. Durvalumab is an immunotherapy option that has shown to more than double overall survival at two years when used in combination with the existing chemotherapy standard of care, cisplatin and gemcitabine. In addition, it reduces the risk of death by up to 24%.”

There remains a significant unmet need for new treatment options in biliary tract cancer and today’s decision marks the first advance in the first-line setting in over ten years.^[5] Durvalumab has been granted an Innovation Passport in Great Britain based on this specific indication. This means durvalumab is eligible for inclusion in the Innovative Licensing and Access Pathway (ILAP).²

Results from the primary endpoint of the TOPAZ-1 Phase III trial showed that durvalumab, in combination with standard-of-care chemotherapy (cisplatin and gemcitabine) demonstrated a clinically meaningful and durable overall survival (OS) benefit as a treatment for patients with advanced biliary tract cancer.³ Updated median OS was 12.9 months compared to 11.3 months with chemotherapy alone.³ More than double the number of patients were estimated to be alive at two years versus chemotherapy alone (23.6% versus 11.5%).³

Ed Piper, Medical and Scientific Affairs Director, AstraZeneca UK, said: “Approval of durvalumab paves the way for a much-needed, new treatment option to improve outcomes for patients with locally advanced, unresectable, or metastatic biliary tract cancer. We’re delighted that the approval of durvalumab was achieved under Project Orbis, an innovative regulatory assessment pathway. We will continue to collaborate with NICE, the SMC and NHS England to secure patient access at the earliest opportunity.”

Data from TOPAZ-1 also show enhanced clinical efficacy after an additional 6.5 months of follow-up for durvalumab plus chemotherapy (gemcitabine plus cisplatin), demonstrating a 24% reduction in the risk of death versus chemotherapy alone [HR 0.76, 95% CI (0.64-0.91)].³

Durvalumab plus chemotherapy was generally well-tolerated in the TOPAZ-1 trial. Grade 3 or 4 treatment-related adverse events (AEs) were experienced by 60.9% of patients treated with durvalumab and chemotherapy, and by 63.5% of patients receiving chemotherapy alone.³ Durvalumab plus chemotherapy did not increase the discontinuation rate due to AEs compared to chemotherapy alone (8.9% for the durvalumab combination versus 11.4% for chemotherapy).^3.

The most common adverse events were anaemia (48.2%), nausea (40.2%), constipation (32.0%), and neutropenia (31.7%) in the durvalumab plus chemotherapy group and anaemia (44.7%), nausea (34.2%), and decreased neutrophil count (31.0%) in the placebo plus chemotherapy group.^[6]

[1] GOV.UK. Guidance on Project Orbis: what the Project Orbis initiative is and MHRA involvement in this regulatory path. Available from: https://www.gov.uk/guidance/guidance-on-project-orbis. Last accessed: February 2023.

[2] GOV.UK. Innovative Licensing and Access Pathway. Available at: https://www.gov.uk/guidance/innovative-licensing-and-access-pathway. Last accessed: February 2023.

[3] Oh D-Y, et al. Updated overall survival from the Phase 3 TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in patients with advanced biliary tract cancer. Poster 56P. Presented at the 2022 ESMO Virtual Plenary Session, 16–18 March 2022.

[4] Electronic Medicines Compendium (EMC). Imfinzi 50 mg/mL concentrate for solution for infusion - Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/9495/smpc#gref. Last accessed: February 2023.

[5] Survival for bile duct cancer. Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/survival. Last accessed: February 2023.

[6] Oh D-Y, et al. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evidence. 2022;1(8).