On November 14, 2023 Astrazeneca reported that Imfinzi (durvalumab) has been approved in China for the 1st-line treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine and cisplatin) (Press release, AstraZeneca, NOV 14, 2023, View Source [SID1234637577]).

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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.