AstraZeneca recently updated initial results from the ATLANTIC clinical trial of durvalumab as third-line or later stage treatment for patients with locally advanced or metastatic programmed death ligand-1 positive non-small cell lung cancer (NSCLC), who lack the epidermal growth factor receptor (EGFR) or have ALK alterations. Preliminary data from this difficult-to-treat patient group demonstrated the drug’s clinical activity with an established safety profile and durable responses.
Durvalumab (MEDI4736) is a human monoclonal antibody targeting programmed cell death ligand 1 (PD-L1), whose signals help tumors escape immune system detection. Durvalumab was developed to block these signals, contradicting the tumor’s immune-evading tactics.
Platinum-based doublets are standard of care first-line treatment for advanced NSCLC, but durable benefit are rare as resistance to chemotherapy invariably develops. The blockade of immune checkpoints is a promising novel approach in cancer treatment. Blocking co-inhibitory molecules, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), from binding to their ligands may restore patients’ T-cell responses against tumors.
ATLANTIC (NCT02087423) is a Phase 2, non-comparative, open label, multicenter, international study assessing the efficacy, safety, and tolerability of durvalumab in about 450 patients with locally advanced or metastatic NSCLC (Stage 3B-4) who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen, and who have limited treatment options.
A full assessment of the results is ongoing, and will be presented at a scientific conference in 2016. Sean Bohen, executive vice president, Global Medicines Development, and chief medical officer at AstraZeneca, said in a recent press release: “As we have seen in other studies, durvalumab has demonstrated expected clinical activity and durable response in these heavily pre-treated patients. As previously communicated, the treatment and regulatory landscape in lung cancer is evolving. We now believe it is unlikely that ATLANTIC can be used for regulatory submission as a monotherapy, but we will make that determination following a full analysis of the data. Durvalumab is a cornerstone of our immuno-oncology portfolio with a fast advancing development programme focused primarily on novel combinations.”
A full durvalumab registration program is ongoing through multiple tumor types, disease stages, and therapy lines both as monotherapy and combined treatment. AstraZeneca’s late-stage immuno-oncology program includes with over 9,000 patients taking part in 16 clinical trials into lung, bladder, head & neck, and other cancers.