Another green light appears to be coming ever closer to AstraZeneca’s Emerald program after a combination therapy featuring the company’s immunotherapy duo Imfinzi and Imjud showed efficacy in certain liver cancer patients.
Results from the phase 3 Emerald-3 trial showed that transarterial chemoembolization (TACE) and combination therapy in combination with Lenvima significantly improved progression-free survival (PFS) compared with TACE alone in patients with unresectable locoregional hepatocellular carcinoma. Lenvima is a multikinase inhibitor marketed by Merck & Co. and Eisai.
However, it remains to be seen whether AZ won the gold medal in Emerald-3. Overall survival (OS), a secondary endpoint that is an important consideration for the FDA, was immature at the time of the interim analysis, but AZ emphasized an improving trend in its April 2nd announcement.
In two ways, the Emerald-3 results are similar to the Emerald-1 results in AZ in the same local treatment setting in liver cancer patients eligible for TACE.
Two years ago, the Emerald-1 trial met its primary endpoint, showing that a cocktail of Imfinzi, Avastin, and TACE reduced the risk of progression or death by 23% compared to TACE alone. At the time, OS was also in its infancy, and Dr. Susan Galbraith, AZ’s head of oncology research and development, cautioned that patient survival data was critical in this regional setting.
Case in point: Despite the PFS win, Merck & Co. received similar liver cancer approval last year after its Keytruda Lenvima TACE therapy failed to improve OS compared to TACE alone.
Emerald-1 has not yet reported final OS data and the study has not been phased into the regulatory filing batch with AZ’s most recent earnings report in February.
Additionally, like Emerald-1, Emerald-3 has a second experimental arm. In this cohort, Imfinzi, Imjud, and TACE without Lenvima showed what AZ called a “strong trend” toward improved PFS and OS, but these analyzes were not formally tested.
Previously in Emerald-1, only the Avastin-containing triplet won TACE, and Imfinzi-TACE failed to move the needle.
Galbraith said in an April 2 statement that AZ is consulting with global regulators about the latest data on Emerald 3, pending final results from the trial’s key secondary endpoints.
Regarding Emerald-1, an AZ spokesperson said the company will share additional data in the future and update its regulatory discussion plans as necessary.
Liver cancer helped AZ’s CTLA-4 drug Imjud enter the market in 2022 as part of a combination with Imfinzi for unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.
Patients who are candidates for embolization are in the early stages of the disease. According to data cited by AZ, more than 200,000 patients will be in this category in 2026. However, most patients who undergo this surgery experience progression or recurrence within 6 to 10 months.
The British pharmaceutical company also owns the third Emerald. The phase 3 trial, called Emerald-2, is testing Imfinzi in combination with Avastin in adjuvant liver cancer, with data expected in late 2026.
Regarding the Imfinzi and Imjud combination, AZ is also expecting results this year from the Nile trial for first-line metastatic bladder cancer and the Volga trial evaluating neoadjuvant therapy for cisplatin-ineligible muscle-invasive bladder cancer. Both companies need to meet the high expectations posed by the combination of Merck & Co.’s Keytruda and Pfizer and Astellas’ antibody-drug conjugate Padocef.
Regarding AZ’s broader oncology portfolio, the company is gearing up for an FDA advisory committee meeting that will delve into two separate applications for its oral SERD treatment cammistrant and its AKT inhibitor Truqap. The results of the Avanzar test conducted by Datroway, which is affiliated with Daiichi Sankyo, are also scheduled to be announced this year for non-small cell lung cancer, which is a first-line treatment.
