AstraZeneca's Imfinzi and Tremelimumab Combination Fails in Phase III NEPTUNE Trial for First-Line Metastatic NSCLC

Compiled by Fan Dongdong

AstraZeneca has long pinned high hopes on the immuno-oncology combination therapy of Imfinzi and Tremelimumab. Following a major setback last year, another Phase III trial in advanced lung cancer (NEPTUNE) for this combination has also been announced as a failure.

NEPTUNE is a randomized, open-label, multicenter, global Phase III trial. On August 21 (local time), AstraZeneca disclosed that preliminary trial results showed that the immuno-oncology combination therapy of Imfinzi and Tremelimumab failed to extend survival in patients with previously untreated stage IV metastatic non-small cell lung cancer (NSCLC) compared with standard treatment regimens. However, the safety and tolerability profile of the Imfinzi and Tremelimumab combination therapy was consistent with that observed in previous trials.

The full results of the Neptune trial have not yet been fully analyzed, and AstraZeneca stated that they will be fully disclosed at future medical conferences.

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80. Tremelimumab is a potential novel human monoclonal antibody with anti-CTLA-4 activity, which promotes T-cell activation and enhances the immune response against cancer.

In May 2017, Imfinzi received its first accelerated approval from the FDA for the treatment of locally advanced or metastatic urothelial carcinoma (mUC). Currently, Imfinzi has been approved in more than 40 countries, including the United States, for unresectable stage III non-small cell lung cancer.

However, the development path of the combination therapy with Imfinzi and Tremelimumab has been fraught with challenges. In November 2018, AstraZeneca announced the results of the MYSTIC trial evaluating Imfinzi in combination with Tremelimumab for the treatment of stage IV non-small cell lung cancer (NSCLC). MYSTIC was a randomized, open-label, international, multicenter Phase III clinical study assessing Imfinzi plus Tremelimumab or Imfinzi monotherapy versus platinum-based chemotherapy in previously untreated patients with stage IV metastatic NSCLC. The study was conducted across 167 centers in 17 countries worldwide. The results showed that the combination therapy ultimately failed to meet its primary endpoint of improving overall survival, and the trial data from the treatment group were not statistically significant.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80%–85% of all cases. Early-stage NSCLC is primarily treated with surgery, whereas middle- and late-stage disease relies mainly on pharmacological therapy. Consequently, advanced NSCLC has become a critical battleground for PD-(L)1 inhibitors. AstraZeneca aimed to capture the lucrative NSCLC market with Imfinzi; thus, the successive trial failures represent a significant setback for the company.

Reference Source:

1、AZ’ Imfinzi combo fails lung cancer study

2、AstraZeneca's Imfinzi-tremelimumab duo flops another late-stage lung cancer trial