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. (CANOPY-N)

• ClinicalTrials.gov Identifier: NCT03968419
• Recruitment Status: Completed
• First Posted: May 30, 2019
• Last Update Posted: October 4, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: canakinumab; Drug: pembrolizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: November 5, 2019
• Actual Primary Completion Date: April 20, 2022
• Actual Study Completion Date: August 15, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: canakinumab monotherapy; All patients will receive canakinumab (ACZ885) prior to surgery	Drug: canakinumab; Administered subcutaneously; Other Name: ACZ885
Experimental: canakinumab + pembrolizumab; All patients will receive canakinumab (ACZ885) and pembrolizumab prior to surgery	Drug: canakinumab; Administered subcutaneously; Other Name: ACZ885; Drug: pembrolizumab; 200mg administered intravenously every 3 weeks
Experimental: pembrolizumab monotherapy; All patients will receive 2 doses of pembrolizumab prior to surgery	Drug: pembrolizumab; 200mg administered intravenously every 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Major Pathological Response (MPR) rate based on Central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
   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 :

1. 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 ]
   To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab
2. 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 ]
   To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of pembrolizumab
3. 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 ]
   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
4. 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 ]
   To characterize the pharmacokinetics of canakinumab therapy
5. 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 ]
   To characterize the pharmacokinetics of pembrolizumab therapy
6. Surgical feasibility rate [ Time Frame: 4 to 6 weeks after first dose ]
   To assess the rate of the surgical feasibility
7. MPR based on central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
   This will assess the rate of MPR at the time of surgery in all participants randomized to pembrolizumab monotherapy arm based on central review.
8. MPR based on local review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
   This will assess the rate of MPR at the time of surgery in all randomized participants based on local review in each treatment arm.
9. Difference in MPR rate based on central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
   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.
10. MPR rate based on the levels of biomarkers [ Time Frame: From date of randomization to 130 days after last dose of drug ]
    Biomarkers include PD-L1, CD8, hs-CRP, hs-IL-6

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

UCLA Oncology Hematology

La Jolla, California, United States, 92037

United States, Kansas

University of Kansas Medical Center Neurology Dept.

Kansas City, Kansas, United States, 66160

United States, New York

SUNY - Upstate Medical University

Syracuse, New York, United States, 13210

United States, Texas

Methodist Hospital / Methodist Cancer Center

Houston, Texas, United States, 77030

Belgium

Novartis Investigative Site

Bruxelles, Belgium, 1000

Canada, Quebec

Novartis Investigative Site

Montreal, Quebec, Canada, H2W 1T8

France

Novartis Investigative Site

Montpellier cedex 5, Herault, France, 34059

Novartis Investigative Site

Bron, France, 69677

Novartis Investigative Site

Paris, France, 75679

Germany

Novartis Investigative Site

Bad Berka, Germany, 99437

Novartis Investigative Site

Giessen, Germany, 35392

Novartis Investigative Site

Halle (Saale), Germany, 06120

Novartis Investigative Site

Koeln, Germany, 51109

Greece

Novartis Investigative Site

Thessaloniki, Greece, 57001

Japan

Novartis Investigative Site

Kashiwa, Chiba, Japan, 277 8577

Netherlands

Novartis Investigative Site

Breda, Netherlands, 4819 EV

Novartis Investigative Site

Hertogenbosch, Netherlands, 5200

Novartis Investigative Site

Maastricht, Netherlands, 6229 HX

Russian Federation

Novartis Investigative Site

Omsk, Russian Federation, 644013

Novartis Investigative Site

Saint Petersburg, Russian Federation, 197022

Novartis Investigative Site

St Petersburg, Russian Federation, 195271

Spain

Novartis Investigative Site

Jaen, Andalucia, Spain, 23007

Novartis Investigative Site

Oviedo, Asturias, Spain, 33011

Novartis Investigative Site

Madrid, Spain, 28034

Taiwan

Novartis Investigative Site

Taipei, Taiwan, 110

Novartis Investigative Site

Taipei, Taiwan

Turkey

Novartis Investigative Site

Izmir, Turkey

Novartis Investigative Site

Sakarya, Turkey, 54290

Novartis Investigative Site

Sihhiye / Ankara, Turkey, 06100

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03968419
• Other Study ID Numbers: CACZ885V2201C; 2018-004813-42 ( EudraCT Number )
• First Posted: May 30, 2019
• Last Update Posted: October 4, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents