In Advanced Lung Cancer Patients, New Drug Showing Durable Responses and Safety

In Advanced Lung Cancer Patients, New Drug Showing Durable Responses and Safety

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.