Dr Spira on the Ongoing PACIFIC-8 Trial in Unresectable Stage III NSCLC

Alexander I. Spira, MD, PhD, FACP, co-director, Virginia Cancer Specialists Research Institute, director, Thoracic and Phase I Program, clinical assistant professor, Johns Hopkins School of Medicine, discusses the ongoing phase 3 PACIFIC-8 trial (NCT05211895) of durvalumab (Imfinzi) in combination with domvanalimab (AB154) following concurrent chemoradiotherapy in patients with unresectable stage III non–small cell lung cancer (NSCLC).

Patients with stage III lung cancer have derived a benefit from durvalumab consolidation therapy, Spira begins. Long-term follow-up data have shown that concurrent chemoradiation followed by 1 year of treatment with durvalumab has increased chances of cure for this patient population, Spira emphasizes. Despite this observed benefit, investigators are still aiming to improve chances of response and cure for these patients, and the PACIFIC-8 study is aiming to address this need, Spira says.

PACIFIC-8 is a randomized trial evaluating patients with stage III lung cancer who have a PD-L1 expression of at least 1% and EGFR or ALK wild-type disease. At least 2 cycles of platinum-based chemotherapy with concurrent radiotherapy are also required. Patients are being randomly assigned to receive 1500 mg of durvalumab plus 20 mg/kg of domvanalimab once every 4 weeks, or durvalumab plus placebo.

Domvanalimab is an anti-TIGIT monoclonal antibody, and prior data have shown that the addition of TIGIT inhibition to PD-1 or PD-L1 inhibition could produce synergistic effect in patients with PD-L1–positive tumors. The goal of PACIFIC-8 is to continue to improve outcomes for a patient population that has benefited from PD-1/PD-L1 inhibition alone, and this could serve as a landmark trial in the treatment of patients with stage III unresectable NSCLC, Spira concludes.