May 07, 2021: “POSEIDON was a Phase III trial of AstraZeneca’s Imfinzi (durvalumab) plus platinum-based chemotherapy or Imfinzi, tremelimumab and chemotherapy versus chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).
Positive high-level results from the final analysis of POSEIDON showed the combination of Imfinzi, tremelimumab and chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit versus chemotherapy alone.
This immunotherapy combination also demonstrated a statistically significant improvement in progression-free survival (PFS) versus chemotherapy alone, as previously reported in October 2019.
Patients in this arm were treated with a short course of tremelimumab, an anti-CTLA4 antibody, over a 16-week period in addition to Imfinzi and standard chemotherapy.
The Imfinzi plus chemotherapy arm demonstrated a statistically significant improvement in PFS versus chemotherapy in the previous analysis, but the OS trend observed in this analysis did not achieve statistical significance. Patients in the control arm were treated with up to six cycles of chemotherapy, while those in the experimental arms were treated with up to four cycles.
Each combination demonstrated an acceptable safety profile, and no new safety signals were identified. The combination with tremelimumab delivered a broadly similar safety profile to the Imfinzi and chemotherapy combination and did not lead to an increased discontinuation of treatment.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “We are pleased to see the POSEIDON Phase III trial demonstrate, for the first time, a significant and clinically meaningful overall survival benefit for Imfinzi plus tremelimumab with chemotherapy in metastatic non-small cell lung cancer. We were particularly pleased by the safety profile.
We’ve seen encouraging uptake of novel combinations in this setting and believe this new approach will add a further option for patients with high unmet medical need. We look forward to discussing next steps with regulatory authorities.”
The data will be presented at a forthcoming medical meeting.
Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy and is the global standard of care based on the PACIFIC Phase III trial.
Imfinzi is also approved in the US, the EU, Japan and many countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial.
Imfinzi is being further assessed across all stages of lung cancer as part of an extensive Immuno-Oncology programme across NSCLC and SCLC, as well as in other tumour types.
The combination of Imfinzi and tremelimumab is being tested in lung cancer, bladder cancer and liver cancer settings.
Stage IV NSCLC
Lung cancer is the leading cause of cancer death accounting for about one-fifth of all cancer deaths.
Patients are commonly diagnosed at Stage IV, when the tumour has spread outside of the lung.
Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC.
Within NSCLC, patients are classified as squamous, representing 25-30% of patients, or non-squamous, the most common type representing approximately 70-75% of NSCLC patients.
Stage IV is the most advanced form of lung cancer and is often referred to as metastatic disease.
The POSEIDON trial was a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy or Imfinzi, tremelimumab and chemotherapy versus chemotherapy alone in the 1st-line treatment of 1,013 patients with metastatic NSCLC.
The trial population included patients with either non-squamous or squamous disease and the full range of PD-L1 expression levels.
POSEIDON excluded patients with certain epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions.
In the experimental arms, patients were treated with a flat dose of 1,500mg of Imfinzi with up to four cycles of chemotherapy once every three weeks or Imfinzi and 75mg of tremelimumab with chemotherapy, followed by maintenance treatment with Imfinzi, or Imfinzi and one dose of tremelimumab on a once-every-four-weeks dosing schedule.
In comparison, the control arm allowed up to six cycles of chemotherapy.
Pemetrexed maintenance treatment was allowed in all arms in patients with non-squamous disease if given during the induction phase.
Primary endpoints included PFS and OS for the Imfinzi plus chemotherapy arm. Key secondary endpoints included PFS and OS in the Imfinzi plus tremelimumab and chemotherapy arm.
As both PFS endpoints were met for Imfinzi plus chemotherapy and Imfinzi, tremelimumab and chemotherapy, the prespecified statistical analysis plan allowed for independent OS testing for the Imfinzi plus tremelimumab and chemotherapy arm.
The trial was conducted in more than 150 centres across 18 countries, including the US, Europe, South America, Asia and South Africa.”