Positive results from the Phase III trial showed that AstraZeneca’s Imfinzi and tremelimumab, when added to platinum-based chemotherapy, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).
“The POSEIDON data offer patients further benefit from Imfinzi and are an important validation of our development strategy to explore novel combinations. Adding a short course of tremelimumab to Imfinzi for those patients already receiving chemotherapy, reduced the risk of cancer progressing or death by 28% compared to chemotherapy alone. The results also showed the significant survival improvement did not compromise tolerability in the 1st-line treatment of patients with metastatic non-small cell lung cancer. We look forward to discussing these data with regulatory authorities,” says Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca.
Patients treated with a short course of five cycles of tremelimumab, an anti-CTLA4 antibody, over 16 weeks in addition to Imfinzi and chemotherapy experienced a 23% reduction in the risk of death versus a range of chemotherapy options (based on a hazard ratio [HR] of 0.77; 95% CI 0.65-0.92; p=0.00304). Median OS was 14.0 months versus 11.7 months for chemotherapy. An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI 0.60-0.86; p=0.00031) with a median PFS of 6.2 months versus 4.8 months, respectively. The combination delivered a broadly similar safety profile to the Imfinzi and chemotherapy combination and did not lead to an increased discontinuation of treatment.
POSEIDON also tested the combination of Imfinzi plus chemotherapy, which demonstrated a statistically significant improvement in PFS (HR=0.74; 95% CI 0.62-0.89; p=0.00093) versus chemotherapy alone. A positive OS trend observed for Imfinzi plus chemotherapy did not achieve statistical significance.
The safety profile of each Imfinzi combination was consistent with the known profiles of the individual medicines, and no new safety signals were identified. Grade 3 or 4 treatment-related adverse events were experienced by 51.8% of patients treated with Imfinzi, tremelimumab and chemotherapy and by 44.6% of patients treated with Imfinzi plus chemotherapy, versus 44.4% for chemotherapy. Treatment-related adverse events led to treatment discontinuation in 15.5% of patients treated with Imfinzi, tremelimumab and chemotherapy and 14.1% of patients treated with Imfinzi plus chemotherapy, versus 9.9% for chemotherapy.
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 development programme across NSCLC and SCLC, as well as in other tumour types. The combination of Imfinziand tremelimumab is being tested in lung cancer, bladder cancer and liver cancer settings.