AZ’s Imfinzi combination shows promise in liver cancer

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Since its first approval in 2017, more than 100,000 patients have been treated with AstraZeneca Imfinzi’s monoclonal antibody (durvalumab), primarily in non-small cell lung cancer.

However, new data from the ongoing HIMALAYA Phase 3 trial offers hope for patients with the most common form of liver cancer, hepatocellular carcinoma (HCC), where surgery cannot remove all of it. of the tumor.

HIMLAYA used a new dose and a new schedule that allowed patients to receive a single “priming” dose of AstraZeneca’s experimental human monoclonal antibody, tremelimumab, then Imfinzi every four weeks. Tremelimumab blocks the activity of the T cell-associated cytotoxic protein 4 (CTLA-4), activating the immune response to cancer and promoting cancer cell death.

Using this STRIDE regimen – Single Tremelimumab at Regular Interval Durvalumab – the trial demonstrated a statistically and clinically significant overall survival benefit compared to sorafenib.

HCC accounts for 75% of all primary liver cancers and is the third leading cause of cancer death worldwide, with approximately 900,000 people diagnosed each year. Currently, only 7% of patients with advanced disease survive five years.

“This is very exciting news for our patients,” said lead researcher Dr Ghassan Abou-Alfa, attending physician at Memorial Sloan Kettering Cancer Center. “HIMALAYA is the first Phase 3 trial to add a new single priming dose of an anti-CTLA4 antibody to another checkpoint inhibitor, durvalumab. This serves to strengthen the patient’s immune system against their liver cancer, with the aim of maximizing long-term survival with minimal side effects.

The driving force behind this program is the fact that most HCC patients also have cirrhosis, mainly caused by hepatitis – the inflammation associated with chronic liver disease causes immunosuppression and can lead to the development of HCC.

“The unique immune environment of liver cancer clearly warrants the search for drugs that harness the power of the immune system to treat HCC,” said AstraZeneca. “There is a critical unmet need for patients with HCC who face limited treatment options. More than half of patients are diagnosed at advanced stages of the disease, often when symptoms first appear. “

Imfinzi is already used to treat unresectable stage 3 non-small cell lung cancer (NSCLC) and extended stage small cell lung cancer (ES-SCLC) as well as advanced bladder cancer. Last month, AstraZeneca released data from its POSEIDON trial showing that adding Imfinzi and tremelimumab to chemotherapy improves both progression-free and overall survival in patients with metastatic non-squamous NSCLC. .

The company has an extensive development program for Imfinzi plus tremelimumab in patients with NSCLC, SCLC, bladder cancer and liver cancer. Imfinzi is being tested as a sole treatment and in combination with other cancer treatments for a wide range of cancers, including cancers of the lung, bladder, liver, gastrointestinal, cervix and cancer. ovary, as well as other solid tumors.


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