CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB-IIIA NSCLC.

Introduction: Canakinumab is a human monoclonal anti-interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation. Methods: CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and pembrolizumab (200 mg intravenous once every three weeks), either in combination or alone, in patients with early-stage (stage Ib-IIIa) NSCLC. The primary end point was major pathologic response (MPR) rates (≤10% of residual tumor cells) by central pathology review in the arms containing canakinumab. Secondary end points included overall response rates, safety, pharmacokinetics, surgical feasibility rates, and MPR rate in the pembrolizumab arm. The impact of treatment on surgical outcomes was assessed as an exploratory outcome. Results: In total, 88 patients were enrolled: 35 to the canakinumab arm, 35 to the canakinumab + pembrolizumab arm, and 18 to the pembrolizumab arm. One patient (2.9%) in the canakinumab arm (95% confidence interval [CI]: 0.07-14.92), six patients (17.1%) in the canakinumab + pembrolizumab arm (95% CI: 6.56-33.65), and three patients (16.7%) in the pembrolizumab arm (95% CI: 3.58-41.42) achieved MPR. No unexpected safety signals were observed. Of the 84 patients (95.5%) who underwent operation, the prespecified 6-week window was achieved for 72 patients (85.7%). Conclusions: Neoadjuvant treatment with canakinumab alone or combined with pembrolizumab did not improve MPR rates compared with pembrolizumab alone. No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after neoadjuvant immunotherapy was rare.