On December 19, 2022 Astrazeneca reported that The PEARL Phase III trial for Imfinzi (durvalumab) did not achieve statistical significance for the primary endpoints of improving overall survival (OS) versus platinum-based chemotherapy as a monotherapy treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC) whose tumour cells express high levels (25% or more) of PD-L1, or in a subgroup of patients at low risk of early mortality (Press release, AstraZeneca, DEC 19, 2022, View Source [SID1234625376]). There was an improvement in OS with Imfinzi monotherapy, which was clinically meaningful in the subset of patients with PD-L1 tumour expression greater than 50%, a secondary endpoint. The trial was conducted primarily in Asia.

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Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "With PEARL, we set out to answer important scientific questions in the treatment of metastatic non-small cell lung cancer at a time when patient selection for immune checkpoint inhibitors was still evolving. We are encouraged to see patients in the metastatic setting at a higher level of PD-L1 tumour expression demonstrate the most benefit with Imfinzi monotherapy treatment, as is commonly seen in this class. We remain steadfast in our dedication to developing new and improved medicines and regimens for patients with lung cancer across our diverse portfolio."

The safety and tolerability profile for Imfinzi was broadly consistent with the known profile of the medicine, and no new safety signals were identified. The data will be shared in due course.

Notes

Stage IV NSCLC
Lung cancer is the second most common form of cancer globally, with more than two million patients diagnosed in 2020.1 Lung cancer is broadly split into NSCLC and small-cell lung cancer (SCLC), with 80-85% classified as NSCLC.2,3 Within NSCLC, patients are classified as squamous, representing 25-30% of patients, or non-squamous, representing approximately 70-75% of patients.3-5

PEARL
PEARL was a randomised, open-label, multicentre, global Phase III trial of Imfinzi monotherapy versus platinum-based chemotherapy (investigator’s choice) as a 1st-line treatment in patients with metastatic NSCLC.

Eligible patients had tumours expressing high levels of PD-L1, defined as ≥25% of tumour cells (TC). The predominantly Asian trial population included both smokers and non-smokers and patients of squamous and non-squamous histology. PEARL excluded patients with certain epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions.

The two primary endpoints were OS in patients whose tumours expressed high levels of PD-L1 (TC≥25%) and OS in a subgroup of patients identified as being at low risk of early mortality using a model developed by AstraZeneca that evaluates various clinical parameters prior to treatment. The trial included centres in Asia, Europe and Australia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi in combination with Imjudo (tremelimumab) plus platinum-based chemotherapy is approved in the US for the treatment of Stage IV (metastatic) NSCLC based on the POSEIDON Phase III trial. Additionally, Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial. Imfinzi is also approved in the US, the EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer based on the CASPIAN Phase III trial.

In addition to its approved indications in lung cancer, Imfinzi is the only approved immunotherapy in unresectable or metastatic biliary tract cancer and is also approved in unresectable hepatocellular carcinoma in combination with Imjudo. It is also approved for previously treated patients with advanced bladder cancer in several countries.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal cancers, ovarian cancer, endometrial cancer, and other solid tumours.