This was a multicenter, Phase III study designed to evaluate the efficacy and safety of
canakinumab in combination with docetaxel versus placebo in combination with docetaxel,
as second- or third-line treatment. The study included adult subjects with advanced NSCLC
whose disease had progressed after prior treatment with a PD-(L)1 inhibitor. Subjects had
also been pre-treated with platinum-based chemotherapy, either given together with
PD-(L)1 inhibitor or sequentially.
The study consisted of 2 parts:
- Part 1: Safety run-in. This part was conducted to confirm the Recommended Phase 3
Regimen (RP3R) of the canakinumab and docetaxel combination. Participants were
treated for at least 2 complete cycles of treatment (21 days per cycle) for safety
evaluation (DLT-Dose Limiting Toxicities) to define RP3R. Participants from the
safety run-in part were treated until any discontinuation criteria were met. After
treatment discontinuation, all participants were followed for safety evaluations
during the safety follow up period (up to 130 days). Additionally, subjects who
discontinued study treatment without prior documented disease progression continued
efficacy assessments in the efficacy follow-up phase irrespective of the start of
new antineoplastic therapy and until documented progressive disease as per protocol.
After the RP3R was determined, enrollment in this part was closed and additional
participants were enrolled in the randomized part (part 2) of the study. Ongoing
patients from the safety run-in part continued their treatment at the assigned dose
level according to the dose and schedule for the safety run-in part.
- Part 2: Randomized part. The randomized, double-blind, placebo-controlled part of
the study opened after confirmation of the RP3R for the combination of canakinumab
and docetaxel. Participants from the randomized part were treated until any
discontinuation criteria were met as per protocol. After treatment discontinuation,
all participants were followed for safety evaluations during the safety follow up
period (up to 130 days). Additionally, subjects who discontinued study treatment
without prior documented disease progression continued efficacy assessments in the
efficacy follow-up phase irrespective of the start of new antineoplastic therapy and
until documented progressive disease as per protocol.
Based on the lack of efficacy observed in the primary analysis, Novartis decided to halt
canakinumab/placebo treatment. Subjects continued to receive docetaxel if they were
deriving clinical benefit as per investigator assessment until discontinuation
