臨床研究等提出・公開システム

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)

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)

88

Overall, the patients’ demographics were balanced among the 3 treatment arms [Canakinumab monotherapy arm (C arm). Pembrolizumab monotherapy arm (P arm), and Canakinumab + Pembrolizumab arm (C+P arm)]. In C arm (n=35), the mean age of the patient (pt) s was 65.5 years (SD: 9.88), and male was 62.9%, female was 37.1%, and most of race/ethnicity were white (57.1%) or Asian (20.0%). In P arm (n=18), the mean age of the pts was 66.1 years (SD: 5.61), and male was 50.0%, female was 50.0%, and most of race/ethnicity were white (66.7%) or Asian (11.1%). In C+P arm (n=35), the mean age of the pts was 67.1 years (SD: 6.98), and male was 60.0%, female was 40.0%, and most of race/ethnicity were white (71.4%) or Asian (8.6%).

A total of 163 pts was screened of which 88 pts were randomized (C arm 35pts, P arm 18 pts, C+P arm 35pts). Of 35, 18 and 35 pts in C, P, and C+P arm who started treatment, all pts in C and C+P arm completed treatment period, and 17 pts in P arm completed treatment period. The reason for not completing treatment period was adverse event (AE) (1pt). After treatment completion or discontinuation, all subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).

Overall, the incidence of AEs was similar for each arm [AEs (Not including serious AEs) for C arm 80.00%, P arm 77.78% and C+P arm 77.14%, SAEs for C arm 28.57%, P arm 22.22%, and C+P arm 25.71%]. The most common AEs (Not including serious AEs) (≧10%) in C arm were fatigue and anaemia (25.71% each), decreased appetite (17.14%), nausea, blood bilirubin increased, cough, bilirubin conjugated increased, lymphocyte count decreased and dyspnoea (11.43 each). The most common SAEs (≧5.0%) in C arm were pneumonia (8.57%) and COVID-19(5.71%). In C arm, 3 pts (8.57%) died during the safety follow-up period. The most common AEs (Not including serious AEs) (≧10%) in P arm were fatigue (22.2%), nausea and SARS-CoV-2 test negative (16.67% each), alanine aminotransferase increased, cough, haemoptysis, dry mouth, procedural pain and atrial fibrillation (11.11% each). The most common SAEs (≧5.0%) in P arm were haemothorax, hypothyroidism, upper gastrointestinal haemorrhage, rash and COVID-19 (5.56% each). In P arm, 1 pts (5.56%) died during the safety follow-up period. The most common AEs (Not including serious AEs) (≧10) in C+P arm were cough, dyspnoea, procedural pain and diarrhoea (17.1% each), hyperthyroidism and fatigue (14.29% each), hyperglycaemia and pruitus (11.43% each). There were no frequently reported SAEs (≧ 5%) in C+P arm. In C+P arm, 2 pts (5.71%) died during the safety follow-up period.

The primary endpoint was major pathological response (MPR [1]) rate based on central review. The MPR rate (95% confidence interval) in C arm and C+P arm was 2.9% (0.07 to 14.92) and 17.1% (6.56 to 33.65), respectively. [1] 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.

The study did not meet its primary endpoint of MPR rate in C arms and C+P arm (assessed by the percentage of participants with ≤ 10% residual viable cancer cells), thus in this study C arm and C+P arm did not demonstrate efficacy for NSCLC in the neoadjuvant setting. The safety data are consistent with the known well-characterized safety profile of canakinumab or pembrolizumab.

Yes

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.

Hirano Takamitsu

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku2@novartis.com

Hirano Takamitsu

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku2@novartis.com

completed

Nov. 05, 2019

Interventional

Randomized, open-label

treatment purpose

2

- 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.
- Eastern Cooperative oncology group (ECOG) performance status of 0 or 1.

- 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

Both

Non-small Cell Lung Cancer

investigational material(s)
Generic name etc :
INN of investigational material : canakinumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :
Generic name etc :
INN of investigational material : pembrolizumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :

control material(s)
Generic name etc :
INN of investigational material : pembrolizumab
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :

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

Mar. 04, 2020