AstraZeneca has built the case for Imfinzi in earlier-stage liver cancer with a second phase 3 trial readout in its EMERALD programme.
The new results come from the EMERALD-3 study, testing a combination of PD-L1 inhibitor Imfinzi (durvalumab) with AZ's CTLA4 inhibitor Imjudo (tremelimumab) – as well as Eisai's multikinase inhibitor Lenvima (lenvatinib) – as a first-line treatment for unresectable hepatocellular carcinoma (HCC) patients who are eligible for a procedure known as transarterial chemoembolisation (TACE).
TACE is a commonly used minimally invasive treatment for liver cancer that combines chemotherapy and vascular blockage, designed to cut off the oxygen and nutrient supply to tumours. HCC is the most common form of liver cancer, and around 30% to 40% of cases are candidates for TACE.
Most patients who receive TACE experience disease progression or recurrence within six to ten months, according to AZ.
In EMERALD-3, the Imfinzi/Imjudo/Lenvima regimen achieved a "statistically significant and clinically meaningful" improvement in progression-free survival (PFS) versus TACE alone, as well as a trend towards improved overall survival (OS).
However, Imfinzi and Imjudo plus TACE – without Lenvima – did not show a significant improvement on TACE alone for either PFS or OS. AZ's two checkpoint inhibitors were administered in the STRIDE regimen – standing for Single Tremelimumab Regular Interval Durvalumab.
Another phase 3 study in the programme – EMERALD-1 – was reported in 2024 and looked at Imfinzi plus anti-VEGF antibody bevacizumab as an add-on to TACE. The results showed a significant improvement in PFS for that regimen over TACE alone, but Imfinzi plus TACE was no better than the control group on that measure.
AZ has yet to file for approval of Imfinzi in the frontline setting for earlier-stage HCC, despite its well-established role in more advanced disease. Imfinzi is already approved by the FDA for use in combination with Imjudo for unresectable, advanced HCC.
The delay could reflect discussion that followed the presentation of the EMERALD-1 results – specifically, the possibility that much of the benefit from the triplet regimen might be due to bevacizumab – and speculation that regulators may want to see additional data proving Imfinzi is adding something significant before approval.
AZ said in a statement that it intends to share the EMERALD-3 data with regulatory authorities.
"Dual immunotherapy with durvalumab and tremelimumab in the STRIDE regimen represents a meaningful advance for patients with embolisation-eligible liver cancer, who currently lack systemic treatment options to keep their cancer from progressing or recurring," said the study's lead investigator, Ghassan Abou-Alfa of Memorial Sloan Kettering Cancer Center in the US.
"EMERALD‑3 shows we can now significantly reduce the risk of disease progression with STRIDE as the immunotherapy backbone alongside lenvatinib and TACE," he added.
AZ's third trial in the programme, EMERALD-2, is looking at Imfinzi with or without bevacizumab as adjuvant therapy for HCC patients who are at high risk of recurrence after successful curative surgery or ablation techniques. That study is due to complete later this year.
https://pharmaphorum.com/news/az-claims-another-win-imfinzi-frontline-liver-cancer
