Canopy-2: Phase 3 Study of Canakinumab plus Docetaxel as Second/Third Line Therapy in Locally Advanced/Metastatic NSCLC

Background: Pembrolizumab, a PD-1 inhibitor combined with platinum-based chemotherapy is standard first-line therapy for eligible patients without a targetable mutation, stage IIIB/IV NSCLC. Currently, there is no data to guide treatment following progression on sequential/concomitant use of platinum-based chemotherapy and PD-1 inhibitors. Activation of inflammation and elevated baseline C-reactive protein (CRP) levels are associated with lower response/resistance to immunotherapies. Canakinumab is a high-affinity anti-IL-1β monoclonal antibody that demonstrated a significant reduction in incidence of fatal and nonfatal lung cancer in patients with increased CRP levels (CANTOS study).

Method: CANOPY-2 (NCT03626545) is a multicenter, phase 3 study evaluating safety and efficacy of docetaxel ± canakinumab in patients with squamous/non-squamous, stage IIIB-IV NSCLC. This study includes a safety run-in part (part 1 – open label) to confirm recommended phase 3 regimen (RP3R) to be used in randomized phase 3 part (part 2 – double blind, placebo-controlled). Key inclusion criteria: adult patients pretreated with one prior platinum-based chemotherapy and one prior PD-(L)1 inhibitor therapy for locally advanced/metastatic disease, either together/sequentially and then progressed; ECOG PS0 – 1. In part 1, ~ 9 patients will be enrolled to have at least 6 evaluable patients and ~ 226 patients will be randomized (1 : 1, stratified by number of prior lines of therapy and histology) in part 2 to docetaxel ± canakinumab.

Primary objectives: to confirm RP3R of canakinumab + docetaxel, as determined by incidence of DLTs in first 42 days of administration (part 1) and overall survival (part 2). Secondary objectives are to assess efficacy (overall response rate, disease control rate, duration of response, time to response, progression-free survival by investigator per RECIST v1.1), safety, pharmacokinetics, immunogenicity of canakinumab, and patient reported outcomes. Enrollment is ongoing.