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NCT03968419: CANOPY-N

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.

Terminated Phase 2 Results posted Last updated 20 June 2024
What this trial tests

Phase 2 trial testing Canakinumab in Non-small Cell Lung Cancer in 88 participants. Terminated before completion.

Timeline
5 November 2019
Primary endpoint
20 April 2022
15 August 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment88
Start date5 November 2019
Primary completion20 April 2022
Estimated completion15 August 2022
Sites29 locations across France, Japan, Netherlands, Greece, Russia, Belgium, Taiwan, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Canakinumab Monotherapy and in Combination With Pembrolizumab Based on Central Review Primary · At time of surgery (up to 6 weeks after first dose of study treatment)

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review.

GroupValue95% CI
Canakinumab Monotherapy2.90.07 – 14.92
Canakinumab + Pembrolizumab17.16.56 – 33.65
Canakinumab Antidrug Antibodies (ADA) Prevalence Secondary · Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)

Canakinumab ADA prevalence at baseline was calculated as the percentage of participants who had a canakinumab ADA positive result at baseline

GroupValue95% CI
Canakinumab Monotherapy0
Canakinumab + Pembrolizumab0
Canakinumab ADA Incidence Secondary · From baseline (Predose on Day 1 of Cycle 1) up to 130 days after last dose of study treatment (assessed up to 24.6 weeks). Cycle = 21 days

Canakinumab ADA incidence on treatment was calculated as the percentage of participants who were canakinumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and canakinumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

GroupValue95% CI
Canakinumab Monotherapy1
Canakinumab + Pembrolizumab0
Pembrolizumab ADA Prevalence Secondary · Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)

Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline

GroupValue95% CI
Canakinumab + Pembrolizumab4
Pembrolizumab Monotherapy3
Pembrolizumab ADA Incidence Secondary · From baseline (Predose on Day 1 of Cycle 1) up to 26 days after last dose of study treatment (assessed up to 10.7 weeks). Cycle = 21 days

Pembrolizumab ADA incidence on treatment was calculated as the percentage of participants who were pembrolizumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and pembrolizumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

GroupValue95% CI
Canakinumab + Pembrolizumab3
Pembrolizumab Monotherapy4
Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1 Secondary · From date of randomization to date of surgery, assessed up to 6 weeks

ORR is defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per local investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters

GroupValue95% CI
Canakinumab Monotherapy00.00 – 10.00
Canakinumab + Pembrolizumab8.61.80 – 23.06
Pembrolizumab Monotherapy11.11.38 – 34.71
Serum Canakinumab Concentration Secondary · Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)

Canakinumab serum concentrations were determined at the specified time points.

Cycle 1
GroupValue95% CI
Canakinumab Monotherapy0± 0
Canakinumab + Pembrolizumab0± 0
Cycle 2
GroupValue95% CI
Canakinumab Monotherapy10.9± 32.9
Canakinumab + Pembrolizumab10.3± 41.0
Serum Pembrolizumab Concentration Secondary · Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)

Pembrolizumab serum concentrations were determined at the specified time points.

Cycle 1 predose
GroupValue95% CI
Canakinumab + Pembrolizumab0± 0
Pembrolizumab Monotherapy0± 0
Cyle 1 0.5 hours post dose
GroupValue95% CI
Canakinumab + Pembrolizumab65.5± 23.8
Pembrolizumab Monotherapy65.5± 19.9
Cycle 2 predose
GroupValue95% CI
Canakinumab + Pembrolizumab16.0± 43.4
Pembrolizumab Monotherapy35.5± 13.7
Surgical Feasibility Rate Secondary · Up to 6 weeks after first dose

Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.

GroupValue95% CI
Canakinumab Monotherapy91.476.94 – 98.20
Canakinumab + Pembrolizumab97.185.08 – 99.93
Pembrolizumab Monotherapy10081.47 – 100.00
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review Secondary · At time of surgery (up to 6 weeks after first dose)

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects randomized to pembrolizumab monotherapy arm based on central review.

GroupValue95% CI
Pembrolizumab Monotherapy16.73.58 – 41.42
Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review Secondary · At time of surgery (up to 6 weeks after first dose of study treatment)

MPR was defined as the percentage of participants with ≤10% residual viable tumor cells on surgical samples. MPR was assessed at the time of surgery based on central review. The difference in MPR rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review along with the Chang and Zhang confidence interval was assessed.

GroupValue95% CI
Canakinumab + Pembrolizumab17.16.56 – 33.65
Pembrolizumab Monotherapy16.73.58 – 41.42
Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review Secondary · At time of surgery (up to 6 weeks after first dose)

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder. MPR was assessed at the time of surgery in all subjects based on local review.

GroupValue95% CI
Canakinumab Monotherapy00.00 – 10.00
Canakinumab + Pembrolizumab20.08.44 – 36.94
Pembrolizumab Monotherapy22.26.41 – 47.64

Adverse events — posted to ClinicalTrials.gov

Time frame: From day of first dose of study medication to 130 days after last dose of study medication, up to 25.6 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Canakinumab Monotherapy
Serious: 10/35 (29%)
Deaths: 3/35
Canakinumab + Pembrolizumab
Serious: 9/35 (26%)
Deaths: 2/35
Pembrolizumab Monotherapy
Serious: 4/18 (22%)
Deaths: 1/18

Serious adverse events (30 terms)

ReactionSystemCanakinumab MonotherapyCanakinumab + PembrolizumabPembrolizumab Monotherapy
PneumoniaInfections and infestations
COVID-19Infections and infestations
ArrhythmiaCardiac disorders
Cardiac failureCardiac disorders
Myocardial ischaemiaCardiac disorders
HypothyroidismEndocrine disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
Immune-mediated hepatitisHepatobiliary disorders
Bacterial infectionInfections and infestations
EndocarditisInfections and infestations
Infectious pleural effusionInfections and infestations
Pneumonia bacterialInfections and infestations
Pneumonia fungalInfections and infestations
PyopneumothoraxInfections and infestations
Septic shockInfections and infestations
Postoperative respiratory failureInjury, poisoning and procedural complications
Procedural painInjury, poisoning and procedural complications
Toxicity to various agentsInjury, poisoning and procedural complications
HyperglycaemiaMetabolism and nutrition disorders
Acute pulmonary oedemaRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HaemothoraxRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Other adverse events (69 terms — click to expand)

ReactionSystemCanakinumab MonotherapyCanakinumab + PembrolizumabPembrolizumab Monotherapy
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
Procedural painInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HyperthyroidismEndocrine disorders
NauseaGastrointestinal disorders
Bilirubin conjugated increasedInvestigations
Blood bilirubin increasedInvestigations
Lymphocyte count decreasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
SARS-CoV-2 test negativeInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
Atrial fibrillationCardiac disorders
Dry mouthGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
PainGeneral disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
Wound complicationInjury, poisoning and procedural complications
Amylase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood creatinine increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Blood thyroid stimulating hormone decreasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Lipase increasedInvestigations
SARS-CoV-2 test positiveInvestigations
White blood cell count decreasedInvestigations
DysgeusiaNervous system disorders
HeadacheNervous system disorders

Most-reported serious reactions: Pneumonia, COVID-19, Arrhythmia, Cardiac failure, Myocardial ischaemia, Hypothyroidism, Upper gastrointestinal haemorrhage, Immune-mediated hepatitis.

Data from ClinicalTrials.gov NCT03968419 adverse events section.

Sponsor's own description

The purpose of this study was to evaluate the 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 of pembrolizumab as a single agent and the dynamic of the tumor microenvironment changes on treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Lung cancer immunotherapy: progress, pitfalls, and promises.
    Lahiri A, Maji A, Potdar PD, Singh N, et al · · 2023 · cited 737× · PMID 36810079 · DOI 10.1186/s12943-023-01740-y
  2. Next generation of immune checkpoint inhibitors and beyond.
    Marin-Acevedo JA, Kimbrough EO, Lou Y. · · 2021 · cited 401× · PMID 33741032 · DOI 10.1186/s13045-021-01056-8
  3. Immune modulatory effects of oncogenic KRAS in cancer.
    Hamarsheh S, Groß O, Brummer T, Zeiser R. · · 2020 · cited 287× · PMID 33116132 · DOI 10.1038/s41467-020-19288-6
  4. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  5. Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies.
    Gelfo V, Romaniello D, Mazzeschi M, Sgarzi M, et al · · 2020 · cited 135× · PMID 32825489 · DOI 10.3390/ijms21176009
  6. Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.
    Wang Y, Johnson KCC, Gatti-Mays ME, Li Z. · · 2022 · cited 103× · PMID 36031601 · DOI 10.1186/s13045-022-01335-y
  7. Neutrophils in the era of immune checkpoint blockade.
    Faget J, Peters S, Quantin X, Meylan E, et al · · 2021 · cited 94× · PMID 34301813 · DOI 10.1136/jitc-2020-002242
  8. Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions.
    Pansy K, Uhl B, Krstic J, Szmyra M, et al · · 2021 · cited 87× · PMID 34948104 · DOI 10.3390/ijms222413311

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03968419.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing