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This Study Will Evaluate the Effect of Canakinumab or Pembrolizumab Given as Monotherapy or in Combination as Neo-adjuvant Treatment for Subjects With Early Stages NSCLC.

NCT03968419

Description:

Major pathological response (MPR) rate of canakinumab given as a neoadjuvant treatment, either as single agent or in combination with pembrolizumab, in addition to evaluate the MPR rate of pembrolizumab as a single agent. Additionally the dynamics of the tumor microenvironment changes on treatment by comparing pre-, on- and post-treatment samples will be evaluated.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: This Study Will Evaluate the Effect of Canakinumab or Pembrolizumab Given as Monotherapy or in Combination as Neo-adjuvant Treatment for Subjects With Early Stages NSCLC.
  • Official Title: A Randomized, Open-label, Phase II Study of Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Subjects With Resectable Non-small Cell Lung Cancer (CANOPY-N)

Clinical Trial IDs

  • ORG STUDY ID: CACZ885V2201C
  • SECONDARY ID: 2018-004813-42
  • NCT ID: NCT03968419

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
canakinumabACZ885canakinumab + pembrolizumab
pembrolizumabcanakinumab + pembrolizumab

Purpose

Major pathological response (MPR) rate of canakinumab given as a neoadjuvant treatment, either as single agent or in combination with pembrolizumab, in addition to evaluate the MPR rate of pembrolizumab as a single agent. Additionally the dynamics of the tumor microenvironment changes on treatment by comparing pre-, on- and post-treatment samples will be evaluated.

Trial Arms

NameTypeDescriptionInterventions
canakinumab monotherapyExperimentalAll patients will receive canakinumab (ACZ885) prior to surgery
  • canakinumab
canakinumab + pembrolizumabExperimentalAll patients will receive canakinumab (ACZ885) and pembrolizumab prior to surgery
  • canakinumab
  • pembrolizumab
pembrolizumab monotherapyExperimentalAll patients will receive 2 doses of pembrolizumab prior to surgery
  • pembrolizumab

Eligibility Criteria

        Key inclusion criteria:

          -  Histologically confirmed NSCLC stage IB-IIIA (per AJCC 8th edition), deemed suitable
             for primary resection by treating surgeon, except for N2 and T4 tumors.

          -  Subject must be eligible for surgery and with a planned surgical resection in
             approximately 4-6 weeks (after the first dose of study treatment).

          -  A mandatory newly obtained tissue biopsy from primary site is required for study
             enrollment. An archival biopsy is also acceptable if obtained up to 5 months before
             first day of study treatment and if the subject did not go through antineoplastic
             systemic therapies between biopsy collection date and beginning of study treatment.

        Note: Aspirates will not be accepted.

        - Eastern Cooperative oncology group (ECOG) performance status of 0 or 1.

        Key exclusion criteria:

          -  Subjects with unresectable or metastatic disease.

          -  History of severe hypersensitivity reactions to monoclonal antibodies, which in the
             opinion of the investigator may pose an increased risk of serious infusion reaction

          -  Subjects who received prior systemic therapy (including chemotherapy, other
             anti-cancer therapies and any other antibody or drug specifically targeting T-cell
             co-stimulation or immune checkpoint pathways) in the past 3 years before screening

          -  Active autoimmune disease that has required systemic treatment in the past 2 years
             prior to randomization. Control of the disorder with replacement therapy is permitted

          -  Subject with suspected or proven immunocompromised state or infections

        Other protocol-defined inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major Pathological Response (MPR) rate based on Central review
Time Frame:At time of surgery (approximately 4 - 6 weeks after first dose)
Safety Issue:
Description:This will assess the rate of MPR at the time of surgery in all participants randomized to canakinumab alone and in combination with pembrolizumab arms based on central review.

Secondary Outcome Measures

Measure:Antidrug antibodies (ADA) of canakinumab
Time Frame:Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose
Safety Issue:
Description:To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab
Measure:Antidrug antibodies (ADA) of pembrolizumab
Time Frame:Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), at end of treatment and then at 26 days after last dose
Safety Issue:
Description:To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of pembrolizumab
Measure:Overall response rate (ORR) per investigator assessment using RECIST v1.1
Time Frame:From date of randomization to date of surgery up to 6 weeks
Safety Issue:
Description:ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1
Measure:Serum canakinumab concentration
Time Frame:Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose
Safety Issue:
Description:To characterize the pharmacokinetics of canakinumab therapy
Measure:Serum pembrolizumab concentration
Time Frame:Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), end of infusion on Day 1 Cycle 1, at end of treatment and then at 26 days after last dose
Safety Issue:
Description:To characterize the pharmacokinetics of pembrolizumab therapy
Measure:Surgical feasibility rate
Time Frame:4 to 6 weeks after first dose
Safety Issue:
Description:To assess the rate of the surgical feasibility
Measure:MPR based on central review
Time Frame:At time of surgery (approximately 4 - 6 weeks after first dose)
Safety Issue:
Description:This will assess the rate of MPR at the time of surgery in all participants randomized to pembrolizumab monotherapy arm based on central review.
Measure:MPR based on local review
Time Frame:At time of surgery (approximately 4 - 6 weeks after first dose)
Safety Issue:
Description:This will assess the rate of MPR at the time of surgery in all randomized participants based on local review in each treatment arm.
Measure:Difference in MPR rate based on central review
Time Frame:At time of surgery (approximately 4 - 6 weeks after first dose)
Safety Issue:
Description:This will estimate the difference in MPR and posterior probability of the difference in MPR ≥ 10% between participants randomized to canakinumab + pembrolizumab combination and pembrolizumab alone based on central review.
Measure:MPR rate based on the levels of biomarkers
Time Frame:From date of randomization to 130 days after last dose of drug
Safety Issue:
Description:Biomarkers include PD-L1, CD8, hs-CRP, hs-IL-6

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • ACZ885
  • canakinumab
  • pembrolizumab
  • NSCLC
  • non-small cell lung cancer
  • non small cell lung cancer
  • early stage NSCLC
  • squamous
  • non-squamous,
  • MPR
  • major pathological response
  • hs-CRP
  • PD-L1
  • hsCRP
  • surgery
  • neo-adjuvant
  • neo adjuvant
  • CD8
  • hs-IL-6
  • CANOPY

Last Updated

May 6, 2020