AstraZeneca's Imfinzi, tremelimumab combination fails to beat chemotherapy in NSCLC study

AstraZeneca announced Wednesday that the Phase III NEPTUNE study of Imfinzi (durvalumab) in combination with tremelimumab in previously-untreated patients with Stage IV non-small-cell lung cancer (NSCLC) failed to meet its primary endpoint of overall survival (OS) versus standard-of-care platinum-based chemotherapy. José Baselga, executive vice president of oncology R&D, said "we are fully committed to a deep analysis of the vast clinical and biomarker data from this trial to gain further insights."

The study randomised patients with Stage IV NSCLC to receive either the PD-L1 inhibitor Imfinzi in combination with the anti-CTLA4 monoclonal antibody tremelimumab or standard-of-care platinum-based chemotherapy alone as first-line treatment. The company noted that the trial was performed in an all-comers population, and subjects included those with non-squamous or squamous histologies, no EGFR or ALK mutation and the full range of PD-L1 expression levels. The trial's main goal was OS in patients with high blood tumour mutational burden (TMB) of 20 or more mutations per megabase.

AstraZeneca indicated that the safety and tolerability profile for the combination of Imfinzi and tremelimumab was consistent with previous trials. The drugmaker added that it will submit the full results for presentation at a future medical meeting.

The failure of the NEPTUNE study comes after AstraZeneca announced last year that the Phase III MYSTIC trial investigating Imfinzi as monotherapy and in combination with tremelimumab in previously-untreated patients with Stage IV NSCLC failed to significantly improve OS versus standard-of-care platinum-based chemotherapy. Shortly afterwards, the company presented results from the study suggesting that in patients with high TMB, defined as 16 or more mutations per megabase, OS was 16.5 months with Imfinzi plus tremelimumab versus 10.5 months with chemotherapy.

Meanwhile, the combination of Imfinzi and tremelimumab has also failed to significantly improve OS versus standard-of-care chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma who experienced disease progression following platinum-based chemotherapy, regardless of their PD-L1 tumour status.

Imfinzi is approved for unresectable, Stage III NSCLC in more than 40 countries, including the US, EU and Japan. The drug, which generated sales of $338 million in the second quarter, is also approved for previously-treated patients with advanced bladder cancer in a number of markets, including the US.

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