Pharmaceutical Business review

Lung cancer drug Imfinzi improves overall survival at interim analysis in phase III CASPIAN trial

Image: Lung cancer drug Imfinzi has improved overall survival at interim analysis in the phase III CASPIAN trial. Photo: courtesy of AstraZeneca.

A planned interim analysis conducted by an Independent Data Monitoring Committee concluded that the trial has met its primary endpoint by showing a statistically-significant and clinically-meaningful improvement in OS in patients treated with Imfinzi in combination with standard-of-care etoposide and platinum-based chemotherapy options vs. chemotherapy alone. The safety and tolerability for this Imfinzi combination was consistent with the known safety profiles of these medicines.

AstraZeneca will submit these results for presentation at a forthcoming medical meeting.

José Baselga, Executive Vice President, Oncology R&D said: “The Phase III CASPIAN results offer new hope for patients who are facing the devastating diagnosis of small cell lung cancer, and for whom new medicines are urgently needed. This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options.”

CASPIAN is a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy options or the combination of Imfinzi, tremelimumab and chemotherapy vs. chemotherapy alone as a 1st-line treatment for patients with extensive-stage SCLC. The trial will continue to the final analysis of OS for the combination of dual immune checkpoint blockade with chemotherapy. This combination includes tremelimumab, an anti-CTLA4 antibody and potential new medicine, with Imfinzi, an anti-PDL1 antibody, and chemotherapy.

Imfinzi is also being tested following concurrent chemoradiation therapy in limited-stage SCLC in the Phase III ADRIATIC trial.

Imfinzi is approved for unresectable, Stage III non-small cell lung cancer in more than 45 countries, including the US, EU and Japan, based on the Phase III PACIFIC trial.

The CASPIAN trial is a randomised, open-label, multi-centre, global, Phase III trial in the 1st-line treatment of patients with extensive-stage SCLC. The trial compared Imfinzi in combination with etoposide and either cisplatin or carboplatin chemotherapy, or Imfinzi, tremelimumab and chemotherapy vs. chemotherapy alone. In the experimental arms, patients were treated with up to four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and prophylactic cranial irradiation.

The trial is being conducted in more than 200 centres across 22 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint is OS.

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.

About two-thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.3 SCLC is an aggressive, fast-growing cancer that recurs and progresses rapidly despite initial response to platinum-based chemotherapy.Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.

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

Imfinzi is also approved for previously-treated patients with advanced bladder cancer in the US, Canada, Brazil, Australia, Israel, India, United Arab Emirates, Qatar, Macau and Hong Kong.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.

Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer.

Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, bladder cancer, head and neck cancer, liver cancer and blood cancers.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease, lines of therapy and modes of action.

We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa (gefitinib) and Tagrisso (osimertinib) and ongoing Phase III trials FLAURA, ADAURA and LAURA as well as the Phase II exploratory combination trials SAVANNAH and ORCHARD.5-7

Our extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a known genetic mutation which represents up to 50% of all patients with lung cancer. Imfinzi (durvalumab), an anti-PDL1 antibody, is in development as monotherapy (Phase III trials ADJUVANT BR.31, PACIFIC-4, PACIFIC-5, and PEARL) and in combination with tremelimumab and/or chemotherapy (AEGEAN, PACIFIC-2, NEPTUNE, POSEIDON, ADRIATIC and CASPIAN Phase III trials).

Source: Company Press Release