The FDA greenlit AstraZeneca’s tremelimumab in combination with its checkpoint inhibitor Imfinzi as a treatment for patients with unresectable hepatocellular carcinoma.
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The FDA greenlit AstraZeneca’s anti-CTLA-4 antibody tremelimumab in combination with its checkpoint inhibitor Imfinzi as a treatment for patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.
Tremelimumab will be marketed under the brand name Imjudo. The approval marks the first for this asset, which has also been assessed in bladder and lung cancer.
Approval for Imjudo was based on the Phase III HIMALAYA trial that showed a single priming dose of Imjudo combined with Imfinzi reduced the risk of death by 22% compared to Bayer’s Nexavar (sorafenib), a standard-of-care multi-kinase inhibitor.
Data from the Phase III study showed an estimated 31% of patients treated with the combination were still alive after three years. AstraZeneca said that only 20% of patients treated with Nexavar were still alive at the same follow-up duration.
The HIMALAYA trial included 1,324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for localized therapy. In the study, the initial dose of Imjudo and Imfinzi is followed by treatment with Imfinzi every four weeks.
AstraZeneca called this the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab). The study’s primary endpoint was overall survival for the combination treatment versus Nexavar. Key secondary endpoints include overall survival for Imfinzi compared to sorafenib, as well as objective response rate and progression-free survival for the combination and for Imfinzi alone.
When the HIMALAYA trial began, Nexavar was the only available frontline standard of care for advanced HCC in the U.S. Since then, other drugs have been approved for this indication, including Eisai’s Lenvima (Lenvatinib), as well as Genentech’s combination of Tecentriq and Avastin.
“In addition to this regimen demonstrating a favorable three-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease,” Dr. Ghassan Abou-Alfa, attending physician at Memorial Sloan Kettering Cancer Center and principal investigator in the HIMALAYA Phase III trial, said in a statement.
A Triumphant End to a Rocky Journey
AstraZeneca’s development of Imjudo combined with Imfinzi has been something of a rocky road. In 2019, the combination of Imfinzi and tremelimumab failed to meet the primary endpoint of improving overall survival compared to standard-of-care chemotherapy in previously-untreated Stage IV non-small cell lung cancer. Then, in 2020, the combination did not improve overall survival in a Phase III metastatic bladder cancer study.
The combination approach has shined on multiple occasions as well. In addition to the HIMALAYA study, AstraZeneca has touted data seen in the Phase III POSEIDON trial.
At the European Society of Medical Oncology meeting last month, AstraZeneca revealed an exploratory analysis from the POSEIDON trial that showed Imfinzi combined with tremelimumab and chemotherapy demonstrated a sustained improvement in overall survival compared to chemotherapy alone in the first-line treatment for patients with Stage IV (metastatic) non-small cell lung cancer. Based on that data, the combination is now under review by multiple regulatory agencies.
