The combination of durvalumab and tremelimumab did not meet its primary overall survival endpoint compared with platinum-based chemotherapy in patients with previously untreated stage IV non–small cell lung cancer and a high tumor mutational burden, according to final OS results from the phase III NEPTUNE trial.
Jose Baselga, MD, PhD
The combination of durvalumab (Imfinzi) and tremelimumab did not meet its primary overall survival (OS) endpoint compared with platinum-based chemotherapy in patients with previously untreated stage IV nonsmall cell lung cancer and a high tumor mutational burden (TMB), according to final OS results from the phase III NEPTUNE trial.
Full findings from the trial are expected to be submitted for presentation at an upcoming medical meeting.
“We are fully committed to a deep analysis of the vast clinical and biomarker data from this trial to gain further insights to improve immuno-oncology approaches for patients with metastatic nonsmall cell lung cancer,” José Baselga, MD, PhD, executive vice president of oncology research and development, AstraZeneca, said in a statement.
NEPTUNE is a randomized, open-label, multicenter, global phase III trial that explored the combination of durvalumab and tremelimumab versus platinum-based chemotherapy as a frontline treatment for patients with metastatic NSCLC (NCT02542293).
The trial, which was conducted in more than 200 centers across 29 countries, included patients with both squamous and nonsquamous disease regardless of PD-L1 expression levels and TMB status. However, patients with activatingEGFRorALKalterations were not eligible, nor were patients with brain metastases, spinal cord compressions, or autoimmune or inflammatory disorders.
Patients were randomized in the trial 1:1 to either receive the PD-L1/CTLA-4 inhibitor combination or standard-of-care chemotherapy.
Although the trial enrolled patients regardless of their TMB status, the primary endpoint was OS among patients whose blood TMB was ≥20 mutations per megabase. Secondary endpoints included OS among the intent-to-treat population and other TMB subgroups as well as progression-free survival (PFS), objective response rate (ORR), second PFS, pharmacokinetics, and immunogenicity of the combination. ORR, PFS, and OS will also be further examined across subgroups of patients according to PD-L1 levels and by additional blood TMB levels.
Safety and tolerability profiles for the combination was consistent with previous reports of the agents, according to the statement.
Durvalumab is undergoing further investigation as a monotherapy in the phase III PEARL trial and in combination with chemotherapy plus or minus tremelimumab in the phase III POSEIDON trial, both in patients with stage IV NSCLC. The PD-L1 inhibitor has been approved by the FDA for the treatment of patients with stage III NSCLC whose disease has not progressed following concurrent chemoradiation.
Update on the Phase III NEPTUNE trial of Imfinzi plus tremelimumab in Stage IV non-small cell lung cancer [press release]. AstraZeneca. Posted August 21, 2019. https://bit.ly/2Zdd5Zu. Accessed August 21, 2019.