A pair of immune checkpoint inhibitors that work in different ways, with or without a targeted therapy, slowed disease progression and may improve survival when added to transarterial chemoembolization (TACE) for the treatment of inoperable liver cancer, according to late-stage study results presented at the American Society of Clinical Oncology Annual Meeting (ASCO 2026).

“These findings are likely to influence clinical practice and may be considered practice-changing for medical oncologists treating hepatocellular carcinoma globally,” ASCO expert Vishwanath Sathyanarayanan, MD, DM, of Apollo Hospitals in Bangalore, India, said in a news release.

Over years or decades, chronic hepatitis B or hepatitis C, metabolic dysfunction-associated steatotic liver disease, heavy alcohol consumption and other causes of liver injury can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the most common type of liver cancer.

HCC is often detected late, when it is difficult to treat. The global standard of care for patients with intermediate-stage cancer that has not spread beyond the liver but cannot be surgically removed is TACE, which delivers chemotherapy and embolization agents directly into the artery supplying the liver. Around a third of people with HCC are eligible for TACE, but about 80% go on to experience disease progression.

“In the embolization-eligible setting for hepatocellular carcinoma, transarterial chemoembolization has been the most practiced global standard of care for over two decades,” said presenter Ghassan Abou-Alfa, MD, PhD, of Memorial Sloan Kettering Cancer Center. “However, outcomes remain poor, with a median progression-free survival of eight to ten months. Repeated TACE procedures wane in effect over time and risk further decline in liver function. Currently there are no systemic therapy-based options approved for these patients globally.”


In the international Phase III EMERALD-3 trial (NCT05301842), Abou-Alfa and colleagues assessed whether adding an immunotherapy combination dubbed STRIDE, with or without Lenvima (lenvatinib), could delay disease progression and improve survival when added to TACE.

The STRIDE regimen consists of a single dose of Imjudo (tremelimumab) plus Imfinzi (durvalumab) given at regular intervals. Imfinzi is a PD-1 immune checkpoint inhibitor that unleashes T-cell activity against tumors, while Imjudo is a CTLA-4 inhibitor that promotes T-cell replication. Imfinzi plus Imjudo is approved for patients with advanced liver cancer who are not eligible for local therapies like TACE. A similar PD-1 and CTLA-4 inhibitor combination, Opdivo (nivolumab) plus Yervoy (ipilimumab), is approved for advanced HCC and several other types of cancer. Lenvima, a targeted therapy that blocks proteins that play a role in cancer growth and formation of blood vessels that supply tumors, is also approved for unresectable HCC.

EMERALD-3 included 760 participants with embolization-eligible HCC in more than 20 countries in North America, South America, Europe and Asia. A majority were Asian, and the median age was approximately 65 years. They were randomly assigned to receive STRIDE plus Levima plus TACE, STRIDE plus TACE without Lenvima or TACE alone. Imfinzi and Lenvima were given for up to three years until patients experienced disease progression or unacceptable toxicity.

Triple therapy was association with delayed disease progression. Patients assigned to STRIDE, Lenvima and TACE had a median progression-free survival (PFS) time of 13.0 months, compared with 9.8 months in the TACE-only group—a 30% reduction in the risk of disease progression or death. 

At this interim analysis, the median overall survival (OS) times were 39.5 months versus 34.7 months, respectively, and the OS rates were 67% versus 62%, suggesting a benefit in the triple therapy group. The study is ongoing, and the patients are being followed for final OS analyses.

STRIDE and TACE without lenvatinib also showed a benefit in a secondary analysis. People who received the dual therapy had a median PFS time of 12.9 months, compared with 8.1 months for the first 175 participants assigned to TACE alone. While PFS time was about the same with or without Lenvima, an exploratory analysis appeared to favor triple therapy for those whose liver cancer was not due to viral hepatitis.

As expected, more intensive combination therapy led to more side effects. Severe or life-threatening (grade 3 or 4) adverse events were reported for 71% of patients in the triple therapy group and 64% of those assigned to STRIDE plus TACE without Lenvima, compared with 29% in the TACE-only group.

“The EMERALD-3 trial represents a meaningful advance for patients, with nearly one in three alive and progression-free at two years when treated with this dual immunotherapy regimen with or without lenvatinib, with a trend toward improved survival,” Abou-Alfa concluded.

Considering the side effects, however, quality-of-life data are still needed to inform practice, according to Stephen Chan, MBBS, MD, of the Chinese University of Hong Kong, who commented on the findings at the conference.

“We need to see how our patients feel about this combination,” he said. “This will help us make a decision about whether the additional toxicity is a worthwhile price to pay for our patients.”

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