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.

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03968419

Collaborator

(none)

Enrollment

Locations

Arms

33.4

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Nov 5, 2019

Actual Primary Completion Date :

Apr 20, 2022

Anticipated Study Completion Date :

Aug 18, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: canakinumab monotherapy All patients will receive canakinumab (ACZ885) prior to surgery	Drug: canakinumab Administered subcutaneously Other Names: ACZ885
Experimental: canakinumab + pembrolizumab All patients will receive canakinumab (ACZ885) and pembrolizumab prior to surgery	Drug: canakinumab Administered subcutaneously Other Names: 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

Arm

Intervention/Treatment

Experimental: canakinumab monotherapy

All patients will receive canakinumab (ACZ885) prior to surgery

Drug: canakinumab

Administered subcutaneously

Other Names:

ACZ885

Experimental: canakinumab + pembrolizumab

All patients will receive canakinumab (ACZ885) and pembrolizumab prior to surgery

Drug: canakinumab

Administered subcutaneously

Other Names:

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

Major Pathological Response (MPR) rate based on Central review [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

Antidrug antibodies (ADA) of canakinumab [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
Antidrug antibodies (ADA) of pembrolizumab [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
Overall response rate (ORR) per investigator assessment using RECIST v1.1 [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
Serum canakinumab concentration [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
Serum pembrolizumab concentration [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
Surgical feasibility rate [4 to 6 weeks after first dose]
To assess the rate of the surgical feasibility
MPR based on central review [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.
MPR based on local review [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.
Difference in MPR rate based on central review [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.
MPR rate based on the levels of biomarkers [From date of randomization to 130 days after last dose of drug]
Biomarkers include PD-L1, CD8, hs-CRP, hs-IL-6

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	UCLA Oncology Hematology	La Jolla	California	United States	92037
2	University of Kansas Medical Center Neurology Dept.	Kansas City	Kansas	United States	66160
3	SUNY - Upstate Medical University	Syracuse	New York	United States	13210
4	Methodist Hospital / Methodist Cancer Center	Houston	Texas	United States	77030
5	Novartis Investigative Site	Bruxelles		Belgium	1000
6	Novartis Investigative Site	Montreal	Quebec	Canada	H2W 1T8
7	Novartis Investigative Site	Montpellier cedex 5	Herault	France	34059
8	Novartis Investigative Site	Bron		France	69677
9	Novartis Investigative Site	Paris		France	75679
10	Novartis Investigative Site	Bad Berka		Germany	99437
11	Novartis Investigative Site	Giessen		Germany	35392
12	Novartis Investigative Site	Halle (Saale)		Germany	06120
13	Novartis Investigative Site	Koeln		Germany	51109
14	Novartis Investigative Site	Thessaloniki		Greece	57001
15	Novartis Investigative Site	Kashiwa	Chiba	Japan	277 8577
16	Novartis Investigative Site	Breda		Netherlands	4819 EV
17	Novartis Investigative Site	Hertogenbosch		Netherlands	5200
18	Novartis Investigative Site	Maastricht		Netherlands	6229 HX
19	Novartis Investigative Site	Omsk		Russian Federation	644013
20	Novartis Investigative Site	Saint Petersburg		Russian Federation	197022
21	Novartis Investigative Site	St Petersburg		Russian Federation	195271
22	Novartis Investigative Site	Jaen	Andalucia	Spain	23007
23	Novartis Investigative Site	Oviedo	Asturias	Spain	33011
24	Novartis Investigative Site	Madrid		Spain	28034
25	Novartis Investigative Site	Taipei		Taiwan	110
26	Novartis Investigative Site	Taipei		Taiwan
27	Novartis Investigative Site	Izmir		Turkey
28	Novartis Investigative Site	Sakarya		Turkey	54290
29	Novartis Investigative Site	Sihhiye / Ankara		Turkey	06100