Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy

Purpose

This study was designed to evaluate the role of canakinumab in combination with docetaxel in subjects with advanced non-small cell lung cancer (NSCLC) previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy.

Condition

  • Non-Small-Cell Lung

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically confirmed advanced (stage IIIB) or metastatic NSCLC. - Subject had received one prior platinum-based chemotherapy and one prior PD-(L)1 inhibitor therapy for locally advanced or metastatic disease. - Subject with ECOG performance status (PS) of 0 or 1. - Subject with at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 in solid tumors criteria.

Exclusion Criteria

  • Subject who previously received docetaxel, canakinumab (or another IL-1β inhibitor), or any systemic therapy for their locally advanced or metastatic NSCLC other than one platinum-based chemotherapy and one prior PD-(L)1 inhibitor. - Subject with EGFRor ALK positive tumor. - History of severe hypersensitivity reaction to monoclonal antibodies, taxanes or excipients of docetaxel or canakinumab.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Safety run-in part: Canakinumab+docetaxel 		Participants were treated with full doses of docetaxel 75mg/m^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1). Subjects were assessed for at least 2 complete cycles of treatment (21 days per cycle; a total of 42 days) for safety evaluation (DLT) to define RP3R. De-escalation to canakinumab 200 mg subcutaneous every 6 weeks + docetaxel 75 mg/m^2, every 3 weeks could also be considered.
  • Drug: Canakinumab
    Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)
    Other names:
    • ACZ885
  • Drug: Docetaxel
    Docetaxel 75mg/m^2, intravenous, administered on Day 1 of each 21-day cycle
Experimental
Randomized part: Canakinumab + docetaxel 		Participants were treated with canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m^2 every 3 weeks
  • Drug: Canakinumab
    Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)
    Other names:
    • ACZ885
  • Drug: Docetaxel
    Docetaxel 75mg/m^2, intravenous, administered on Day 1 of each 21-day cycle
Placebo Comparator
Randomized part: Placebo + docetaxel 		Participants were treated with placebo subcutaneous at RP3R and docetaxel at 75 mg/m^2 every 3 weeks
  • Drug: Docetaxel
    Docetaxel 75mg/m^2, intravenous, administered on Day 1 of each 21-day cycle
  • Other: Placebo
    Placebo, sub-cutaneous, admnistered at the RP3R defined in Part 1-safety run-in.

More Details

Status
Terminated
Sponsor
Novartis Pharmaceuticals

Study Contact

Detailed Description

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