On November 9, 2023 Astrazeneca reported that Positive high-level results from the EMERALD-1 Phase III trial showed Imfinzi (durvalumab) in combination with transarterial chemoembolisation (TACE) and bevacizumab demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) versus TACE alone in patients with hepatocellular carcinoma (HCC) eligible for embolisation (Press release, AstraZeneca, NOV 9, 2023, View Source [SID1234637288]). The trial continues to follow the secondary endpoint of overall survival (OS).

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Liver cancer, of which HCC is the most common type, is the third-leading cause of cancer death with an estimated 900,000 people worldwide diagnosed each year.1,2 Approximately 20-30% of patients are eligible for embolisation, a procedure that blocks the blood supply to the tumour and can also deliver chemotherapy or radiation therapy directly to the liver.3-9 Despite being the standard of care in this setting, most patients who receive embolisation experience rapid disease progression or recurrence.10-14

Dr. Riccardo Lencioni, Professor and Director of the Cancer Imaging Program in the Department of Diagnostic and Interventional Radiology of Pisa University Hospital in Pisa, Italy, and principal investigator in the trial, said: "Patients with liver cancer eligible for embolisation experience high rates of progression or recurrence and do not have the opportunity for early intervention with effective systemic therapy. These results for durvalumab plus bevacizumab have the potential to reshape the treatment of this complex disease with a poor prognosis by showing for the first time that adding an immunotherapy combination to TACE significantly improves progression-free survival."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These positive results for Imfinzi-based treatment in EMERALD-1 may bring the potential of immunotherapy to patients with earlier stages of liver cancer. We look forward to discussing these data with regulatory authorities and seeing the survival data mature over time, which will be important as we aim to bring this novel treatment option to patients."

The safety profiles for Imfinzi and TACE plus bevacizumab were consistent with the known profile of each medicine, and there were no new safety findings.

The data will be presented at a forthcoming medical meeting and shared with regulatory authorities.

AstraZeneca has an extensive clinical development programme further assessing Imfinzi across multiple gastrointestinal (GI) cancer settings, including in combination with bevacizumab in adjuvant HCC (EMERALD-2) and in combination with Imjudo (tremelimumab), lenvatinib and TACE in embolisation-eligible HCC (EMERALD-3).

Notes

Liver cancer
Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.1-2 Asia holds more than 70% of the world’s new liver cancer cases.15 About 75% of all primary liver cancers in adults are HCC.1 Between 80-90% of all patients with HCC also have cirrhosis.16 Chronic liver diseases such as cirrhosis are associated with inflammation that over time can lead to the development of HCC.16 Immunotherapy is a proven treatment modality in HCC with approved options available for patients in later-line settings.17

EMERALD-1
EMERALD-1 is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial of Imfinzi plus TACE concurrently, followed by Imfinzi with or without bevacizumab until progression versus TACE alone in a total of 616 patients with unresectable HCC eligible for embolisation.

The trial was conducted in 157 centres across 18 countries, including in North America, Australia, Europe, South America and Asia. The primary endpoint was PFS for Imfinzi and TACE plus bevacizumab versus TACE alone, and secondary endpoints include PFS for Imfinzi plus TACE, overall survival, patient-reported outcomes and objective response rate.

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 approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo (tremelimumab) in unresectable HCC in the US, EU, Japan and many other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively.

In addition to its indications in 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.

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, ovarian cancer, endometrial cancer 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, as well as in resectable NSCLC (AEGEAN).

In addition to the EMERALD programme across multiple liver cancer settings, AstraZeneca has ongoing registrational trials investigating Imfinzi in resectable gastric and gastroesophageal junction cancers (MATTERHORN) and in locally advanced oesophageal cancer (KUNLUN). In June 2023, Imfinzi added to standard-of-care neoadjuvant chemotherapy met a key secondary endpoint of pathologic complete response in the MATTERHORN Phase III trial.