The approval by China’s National Medical Products Administration (NMPA) was based on the primary results from the TOPAZ-1 Phase III trial published in the New England Journal of Medicine Evidence, as well as a prespecified exploratory analysis of an additional cohort of patients in China.

BTC is a group of rare and aggressive cancers that occur in the bile ducts (cholangiocarcinoma) and gallbladder.^1,2 An estimated 211,000 new patients are diagnosed with gallbladder and biliary tract cancer each year, and nearly one in five patients diagnosed is in China.^3,4 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.⁵

Shukui Qin, MD, President of Nanjing Tianyinshan Hospital of China Pharmaceutical University and national leading principal investigator of the trial in China, said: "Over the past decade, there has been little progress in the treatment of advanced biliary tract cancer. However, the successful results of the TOPAZ-1 trial confirmed that durvalumab plus routine chemotherapy has statistically significant and clinically meaningful overall survival and progression-free survival benefits for these patients. This approval provides a new and better option for the treatment of these patients in China.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “With this approval for Imfinzi plus chemotherapy, physicians will now be able to offer this global standard-of-care treatment to patients in China, where nearly one in five patients with biliary tract cancer is diagnosed. This important milestone underscores our commitment to bring innovative medicines that transform survival outcomes to people across the globe living with aggressive gastrointestinal tumours such as biliary tract cancer.”

In an interim analysis of the TOPAZ-1 Phase III trial, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). Median OS was 12.8 months versus 11.5 for chemotherapy. Additionally, efficacy results from a prespecified exploratory analysis in an additional cohort of TOPAZ-1 patients enrolled in China were consistent with those in the overall global trial population, showing Imfinzi plus chemotherapy reduced the risk of death by 22% versus chemotherapy alone (HR of 0.78; 95% CI, 0.51-1.18).

In the TOPAZ-1 trial, Imfinzi plus chemotherapy was generally well tolerated, with no new safety signals observed. Safety results in the cohort of Chinese patients were consistent with results in the overall global trial population.

Imfinzi plus chemotherapy is approved in the US, EU (1st-line), Japan and other countries for the treatment of adults with locally advanced or metastatic BTC. Regulatory applications are also currently under review in several other countries based on the TOPAZ-1 results.

Notes

Biliary tract cancer
BTC is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).^1,2

Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.^5-7 Cholangiocarcinoma is more common in China and Southeast Asia and is on the rise in Western countries.^1,5

TOPAZ-1
TOPAZ-1 was a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint was OS and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses. 

Imfinzi is also approved in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC) in the US, EU, Japan and many other countries based on the HIMALAYA Phase III trial.

In addition to its indications in gastrointestinal (GI) cancers, Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial results, which have been confirmed in the real-world setting in the PACIFIC-R study.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small-cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial. Imfinzi is approved in previously treated patients with advanced bladder cancer in a small number of countries. 

Since the first approval in May 2017, more than 200,000 patients have been treated with Imfinzi. 

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, and other solid tumours. In 2023, AstraZeneca announced positive results for Phase III trials including combinations with Imfinzi in ovarian (DUO-O) and endometrial (DUO-E) cancers with Lynparza (olaparib), as well as in resectable NSCLC (AEGEAN) and in liver cancer eligible for embolisation (EMERALD-1). In June 2023, Imfinzi added to standard-of-care neoadjuvant chemotherapy met a key secondary endpoint of pathologic complete responses in the MATTERHORN Phase III trial.

AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.⁸

Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.

In addition to its indications in BTC and HCC, Imfinzi is being assessed in combinations, including with Imjudo, in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.

Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is approved in the US and several other countries for HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. 

Lynparza, a first-in-class PARP inhibitor, is approved the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada). 

AstraZeneca also has a global exclusive license agreement with KYM Biosciences Inc. for AZD0901. AZD0901 is a potential first-in-class antibody drug conjugate targeting Claudin 18.2, a promising therapeutic target in gastric cancer, currently in Phase I development.

AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.

AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as a single treatment and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.

AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. 

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References

1. Marcano-Bonilla L, et al. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. CCO. 2016;5(5).

2. ESMO. What is Biliary Tract Cancer. Available at: https://www.esmo.org/content/download/266801/5310983/1/EN-Biliary-Tract-Cancer-Guide-for-Patients.pdf. Accessed November 2023.

3. Ouyang G, et al. The global, regional, and national burden of gallbladder and biliary tract cancer and its attributable risk factors in 195 countries and territories, 1990 to 2017: A systematic analysis for the Global Burden of Disease Study 2017. Cancer. 2021;127:2238-2250.

4. Chen S, et al. Current status, trends, and predictions in the burden of gallbladder and biliary tract cancer in China from 1990 to 2019. Chin Med J (Engl). 2022;135(14):1697-1706. 

5. Turkes F, et al. Contemporary Tailored Oncology Treatment of Biliary Tract Cancers. Gastroenterol Res Pract. 2019;2019:7698786.

6. Rawla P, et al. Epidemiology of gallbladder cancer. Clin Exp Hepatol. 2019;5(2):93-102.

7. Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557-588.

8. WHO. World Cancer Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed November 2023.

Source:- Astrazeneca