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.

Non-small Cell Lung Cancer Clinical Trial

— CANOPY-N  

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03968419
• Other study ID #: CACZ885V2201C
• Secondary ID: 2018-004813-42
• Status: Terminated
• Phase: Phase 2
• Start date: November 5, 2019
• Est. completion date: August 15, 2022

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 88
• Est. completion date: August 15, 2022
• Est. primary completion date: April 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Canakinumab
200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks
• Pembrolizumab
200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Canada	Novartis Investigative Site	Montreal	Quebec
France	Novartis Investigative Site	Bron
France	Novartis Investigative Site	Montpellier cedex 5	Herault
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Bad Berka
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Halle (Saale)
Germany	Novartis Investigative Site	Koeln
Greece	Novartis Investigative Site	Thessaloniki
Japan	Novartis Investigative Site	Kashiwa	Chiba
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Hertogenbosch
Netherlands	Novartis Investigative Site	Maastricht
Russian Federation	Novartis Investigative Site	Omsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Spain	Novartis Investigative Site	Jaen	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Oviedo	Asturias
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Sakarya
Turkey	Novartis Investigative Site	Sihhiye / Ankara
United States	Methodist Hospital / Methodist Cancer Center	Houston	Texas
United States	University of Kansas Medical Center Neurology Dept.	Kansas City	Kansas
United States	UCLA Oncology Hematology	La Jolla	California
United States	SUNY - Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Greece,  Japan,  Netherlands,  Russian Federation,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	At time of surgery (up to 6 weeks after first dose of study treatment)
Secondary	Canakinumab Antidrug Antibodies (ADA) Prevalence	Canakinumab ADA prevalence at baseline was calculated as the percentage of participants who had a canakinumab ADA positive result at baseline	Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)
Secondary	Canakinumab ADA Incidence	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)	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
Secondary	Pembrolizumab ADA Prevalence	Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline	Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)
Secondary	Pembrolizumab ADA Incidence	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)	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
Secondary	Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1	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	From date of randomization to date of surgery, assessed up to 6 weeks
Secondary	Serum Canakinumab Concentration	Canakinumab serum concentrations were determined at the specified time points.	Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)
Secondary	Serum Pembrolizumab Concentration	Pembrolizumab serum concentrations were determined at the specified time points.	Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)
Secondary	Surgical Feasibility Rate	Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.	Up to 6 weeks after first dose
Secondary	Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review	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.	At time of surgery (up to 6 weeks after first dose)
Secondary	Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review	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.	At time of surgery (up to 6 weeks after first dose of study treatment)
Secondary	Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review	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.	At time of surgery (up to 6 weeks after first dose)
Secondary	Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers	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 rate was analyzed by the biomarker subgroups at baseline. Biomarkers included PD-L1, CD8, hs-CRP and hs-IL-6.	From date of randomization up to 6 weeks after first dose

External Links

•   Plain Language Trial Summary