PACIFIC-2: Phase 3 study of concurrent durvalumab and platinum-based chemoradiotherapy in patients with unresectable, stage III NSCLC.

TPS8573 Background: Durvalumab, a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, is approved in the US, Japan and several other countries, for the treatment of patients (pts) with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent chemoradiotherapy (cCRT). These approvals were based on results from the phase 3 PACIFIC study, in which durvalumab was given 1–42 days after completion of definitive cCRT and significantly improved progression-free survival (PFS) vs placebo (median 16.8 vs 5.6 months; HR 0.52, 95% CI 0.42– 0.65; p<0.001) and overall survival (OS) vs placebo (stratified HR 0.68; 99.73% CI 0.47–0.997; p=0.0025). Increasing evidence suggests additional benefit when anti-PD-1/PD-L1 therapies are administered alongside cCRT. The PACIFIC 2 study therefore aims to assess whether durvalumab plus cCRT provides additional benefit, in terms of PFS and objective response rate (ORR), compared with cCRT alone. Methods: PACIFIC 2 is a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study. Approximately 300 pts with unresectable stage III NSCLC will be randomized (2:1) to receive either durvalumab (intravenous 1500 mg) every 4 weeks (q4w) + cCRT, or placebo q4w + cCRT. Eligible pts must have histologically or cytologically confirmed stage III disease; ECOG performance status 0 or 1; and life expectancy >12 weeks at randomization. Pts who discontinue treatment will be followed for safety and OS. Primary endpoints are PFS and ORR (RECIST v1.1) assessed via blinded independent central review. Secondary endpoints include OS; OS at month 24; complete response (CR) rate; duration of response; disease control rate; time to death/distant metastases; time from randomization to second progression; safety; and symptoms, functioning and global health status. Pts with a CR, partial response or stable disease will continue to receive durvalumab or placebo until clinical or RECIST v1.1-defined disease progression, or until another discontinuation criterion is met. Study enrollment began in March 2018 and recruitment is ongoing. Clinical trial information: NCT03519971.