AstraZeneca Announces Landmark TOPAZ-1 Phase III Results: Imfinzi Plus Chemotherapy Doubles Three-Year Survival Rate in Advanced Biliary Tract Cancer

Apr 16, 2024 14:58 CST Updated 14:58

AstraZeneca

Biopharmaceutical Manufacturer

On April 16, AstraZeneca announcedLatest Exploratory Results from the TOPAZ-1 Phase III Trial.Data shows:Imfinzi(Durvalumab) in combination with standard chemotherapy treatmentPatients with Advanced Biliary Tract Cancer (BTC)The annual overall survival (OS) rate doubled.

The results of the trial will be announced at the 2024 Cholangiocarcinoma Foundation Conference on April 18.This is the longest survival follow-up result reported in a global randomized Phase III trial under equivalent conditions to date.

Imfinzi （durvalumab）It is a human monoclonal antibody that binds to the PD-L1 protein, blocking the interaction between PD-L1 and PD-1 and CD80 proteins, countering the tumor's immune evasion strategy, and releasing the suppression of immune responses.

Previously, Imfinzi in combination with chemotherapy has been approved in multiple countries for the treatment of locally advanced or metastatic biliary tract cancer (BTC), and in combination with Imjudo for unresectable hepatocellular carcinoma (HCC). In Japan and the EU, Imfinzi has also been approved as a monotherapy for unresectable HCC and is approved in a few countries for patients with previously treated advanced bladder cancer.

Currently, Imfinzi is being tested as a monotherapy or in combination with other anticancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, various gastrointestinal cancers, and other solid tumors.

TOPAZ-1 is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial.In a trial involving 685 adult patients with unresectable, locally advanced or metastatic BTC (including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer), Imfinzi combined with chemotherapy (gemcitabine plus cisplatin) was compared to placebo combined with chemotherapy as a first-line treatment. Patients with bladder cancer were excluded.

The primary endpoint is overall survival.，Key secondary endpoints included progression-free survival, objective response rate, and safety. The trial was conducted at 105 centers across 17 countries in the United States, Europe, and South America, as well as in several Asian countries including South Korea, Thailand, Japan, and China.

Over a period of more than three years (median follow-up time was 41.3 months),Results show：Imfinzi Combination chemotherapy reduced the risk of death by 26% compared with chemotherapy alone (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.87).Imfinzi The median OS for combination chemotherapy was 12.9 months, compared to 11.3 months for chemotherapy alone. UsingImfinziThe number of patients surviving after three years was more than double for those on the regimen compared to those receiving chemotherapy alone (14.6% vs. 6.9%).。

Imfinzi in combination with chemotherapyTolerability remained good with longer follow-up, and no new safety signals were observed.The results showed that 15.4% of patients experienced serious treatment-related adverse events after receiving Imfinzi combined with chemotherapy, compared to 17.3% for chemotherapy alone.

October 2021,TOPAZ-1 Trial Met Primary Endpoint of OS in Interim AnalysisThe results showed that, compared with chemotherapy alone, the combination therapy reduced the risk of death by 20% (based on HR of 0.80; 95% CI, 0.66-0.97; two-sided P=0.021 at a statistical significance threshold of 0.03).

Stacie Lindsey, CEO of the Cholangiocarcinoma Foundation, stated"AstraZeneca's longer survival data in advanced biliary tract cancer represents a meaningful milestone, as we are seeing three-year survival data for these patients for the first time."

Biliary Tract Cancer (BTC)Is a group of rare and aggressive gastrointestinal (GI) cancers that form in the bile duct cells (cholangiocarcinoma), gallbladder, or ampulla (where the bile duct and pancreatic duct connect to the small intestine). Approximately 50,000 people are diagnosed with BTC annually in the United States, Europe, and Japan, with about 210,000 diagnosed globally. Historically, these patients have had a poor prognosis, with approximately 5%-15% of BTC patients surviving five years. For those with metastatic disease, the five-year survival rate drops to less than 5%.Bile duct cancer is more common in China and Thailand, and is on the rise in Western countries.