ARCTIC trial in third-line non-small cell lung cancer: Durvalumab monotherapy showed a clinically-meaningful reduction in the risk of death compared to chemotherapy
Results from the phase III ARCTIC trial in patients with locally-advanced or metastatic non-small cell lung cancer ( NSCLC ) who have received at least two prior treatments, were announced.
This randomised, open-label, multi-centre trial assessed the efficacy and safety of the combination of Durvalumab ( Imfinzi ) plus Tremelimumab, as well as Durvalumab and Tremelimumab monotherapies, versus standard-of-care chemotherapy ( SoC ) in patients with PD-L1-low/negative NSCLC ( sub-study B ), and Durvalumab monotherapy versus SoC in patients with PD-L1-high NSCLC ( sub-study A ).
In sub-study B, the combination of Durvalumab plus Tremelimumab in patients with PD-L1 low/negative NSCLC did not meet the primary endpoints of a statistically-significant and clinically-meaningful improvement in progression-free survival ( PFS ) and overall survival ( OS ) compared to SoC.
Activity and safety of monotherapy arms of sub-study B were consistent with prior published data.
Sub-study A was not powered for statistical significance; however, Durvalumab monotherapy showed a clinically-meaningful reduction in the risk of death compared to chemotherapy.
The ARCTIC trial was a randomised, open-label, multi-centre, global phase III trial containing two sub-studies: sub-study A ( 1:1 randomisation of patients with PDL1-high tumours to Durvalumab versus SoC and sub-study B ( 2:3:1:2 randomisation of patients with PDL1-low/negative tumours to Durvalumab monotherapy, Durvalumab plus Tremelimumab or Tremelimumab vs SoC ).
Tumour PD-L1 expression was assessed with the Ventana PD-L1 ( SP263 ) assay with PD-L1 high defined as greater than or equal to 25% of tumour cells with membrane staining.
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.
Tremelimumab is a human monoclonal antibody and potential new medicines 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.
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined. ( Xagena )
Source: AstraZeneca, 2018