Clinical trial NCT03968419: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-05-30
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This was a randomized, phase II, open-label study evaluating canakinumab, an anti-IL-1β monoclonal antibody, or pembrolizumab, a monoclonal antibody designed to block the PD-1 receptor, as monotherapy or in combination as neoadjuvant therapy. The study population included adult subjects with resectable non-small cell lung cancer (NSCLC) planned for surgery in approximately 4-6 weeks. Subjects were treated for a maximum duration of 6 weeks (2 cycles) until surgery, progression, unacceptable toxicity or discontinuation from the study treatment for any other reason.

Subjects were randomized in a 2:2:1 ratio to one of the 3 treatment arms (canakinumab alone or canakinumab in combination with pembrolizumab or pembrolizumab alone). Surgery was performed between 4 to 6 weeks after the first dose of study treatment.

All randomized subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).

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 have been 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 was required for study enrollment. An archival biopsy was 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.
* 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 was permitted
* Subject with suspected or proven immunocompromised state or infections

Primary outcomes:
measure: 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
timeFrame: At time of surgery (up to 6 weeks after first dose of study treatment)
Secondary outcomes:
measure: Canakinumab Antidrug Antibodies (ADA) Prevalence
timeFrame: Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)
measure: Canakinumab ADA Incidence
timeFrame: 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
measure: Pembrolizumab ADA Prevalence
timeFrame: Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)
measure: Pembrolizumab ADA Incidence
timeFrame: 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
measure: Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1
timeFrame: From date of randomization to date of surgery, assessed up to 6 weeks
measure: Serum Canakinumab Concentration
timeFrame: Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)
measure: Serum Pembrolizumab Concentration
timeFrame: Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)
measure: Surgical Feasibility Rate
timeFrame: Up to 6 weeks after first dose
measure: Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review
timeFrame: At time of surgery (up to 6 weeks after first dose)
measure: Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review
timeFrame: At time of surgery (up to 6 weeks after first dose of study treatment)
measure: Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review
timeFrame: At time of surgery (up to 6 weeks after first dose)
measure: Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers
timeFrame: From date of randomization up to 6 weeks after first dose
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCLA Oncology Hematology
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center Neurology Dept.
state: Kansas
city: Syracuse
country: United States
facility: SUNY - Upstate Medical University
state: New York
city: Houston
country: United States
facility: Methodist Hospital / Methodist Cancer Center
state: Texas
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montpellier cedex 5
country: France
facility: Novartis Investigative Site
state: Herault
city: Bron
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Bad Berka
country: Germany
facility: Novartis Investigative Site
city: Giessen
country: Germany
facility: Novartis Investigative Site
city: Halle (Saale)
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Hertogenbosch
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Omsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Jaen
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Sakarya
country: Turkey
facility: Novartis Investigative Site
city: Sihhiye / Ankara
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Garrido P, Pujol JL, Kim ES, Lee JM, Tsuboi M, Gomez-Rueda A, Benito A, Moreno N, Gorospe L, Dong T, Blin C, Rodrik-Outmezguine V, Passos VQ, Mok TS. Canakinumab with and without pembrolizumab in patients with resectable non-small-cell lung cancer: CANOPY-N study design. Future Oncol. 2021 Apr;17(12):1459-1472. doi: 10.2217/fon-2020-1098. Epub 2021 Mar 2.