臨床研究等提出・公開システム

A Phase III, Multicenter, Randomized, Double Blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Canakinumab Versus Placebo as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II -IIIA and IIIB (T>5cm N2) Completely Resected (R0) Non-small Cell Lung Cancer (NSCLC) (CANOPY-A)

Study of Efficacy and Safety of Canakinumab as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) Completely Resected Non-small Cell Lung Cancer (CANOPY-A)

1382

Overall, the patients' demographics were balanced between the two treatment arms. In Canakinumab arm, the mean age of the patients was 61.5 years (SD: 8.90), and male was 62.0%, female was 38.0%, and most of race/ethnicity were white (56.7%) or Asian (35.8%). In Placebo arm, the mean age of the patients was 61.6 years (SD: 9.00), and male was 62.7%, female was 37.3%, and most of race/ethnicity were white (56.7%) or Asian (34.3%).

A total of 1830 patients (pts) were screened of which 1382 participants were randomized to treatment on a 1:1 basis (canakinumab arm 693 pts, placebo arm 689 pts). Of 692 pts in the canakinumab arm and 689 pts in the placebo arm who started treatment, 414 pts and 420 pts completed treatment, respectively, and the most common reasons for not completed treatment in either arm was disease progression (138 pts, 148 pts), followed by study terminated by Sponsor (60pts, 44pts), and adverse events (34pts, 31pts).

Overall, the incidence of adverse event (AE) s was similar for the canakinumab and placebo arms [AEs (Not including serious AEs) for canakinumab arm 67.2% and placebo arm 66.04%, SAEs for canakinumab arm 20.38% and placebo arm 21.19%]. The most common AEs (Not including serious AEs) (>=10%) in canakinumab arm were pyrexia (18.2%), Arthralgia (10.69%), and Fatigue (10.12%). The most common SAEs (>=1.0%) in canakinumab arm were COVID-19 (6.94%), Pneumonia (1.88%), and Dyspnoea (1.01%). In canakinumab arm, 62 patients died during the study. During the on-treatment period, 9 (1.3%) deaths occurred.

The primary endpoint was disease-free survival (DFS) [1] as assessed by the local investigator. The median DFS (95% CI) for canakinumab arm and placebo arm were 35.02 months (28.55 to NA [2]) and 29.73 months (23.72 to NA [2]), respectively. [1] DFS is the time from the date of randomization to the date of the first documented NSCLC disease recurrence as assessed by local investigator radiologically or death due to any cause. Disease recurrence included diagnoses of new primary lung malignancies. Clinical deterioration was not considered as a recurrence of disease. In case of non-conclusive radiological evidence, a biopsy assessment was performed to confirm NSCLC recurrence. The median DFS was estimated using the Kaplan-Meier method. DFS was censored if no DFS event was observed prior to the analysis cut-off date or patients who received any subsequent anti-neoplastic therapy for NSCLC. The censoring date was the date of last assessment before the cut-off date or NSCLC related anti-neoplastic therapy date. [2] NA: Not estimable due to the insufficient number of participants with events

This study was a phase III, multicenter, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult patients with stages AJCC/UICC v. 8 II-IIIA and IIIB completely resected NSCLC. As a result of this study, canakinumab did not prolong DFS compared to placebo. No new safety signals or unexpected safety findings were observed in the patients treated with canakinumab. The overall safety and tolerability profile of canakinumab

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 will be available according to the process described on www.clinicalstudydatarequest.com.

Yamauchi Kyosuke

Novartis Pharma. K.K.

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

rinshoshiken.toroku2@novartis.com

Yamauchi Kyosuke

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

July. 13, 2018

Interventional

Multi center, randomized, double-blinded, placebo-controlled

treatment purpose

3

- Have completely resected (R0) NSCLC AJCC/UICC v. 8 stage IIA-IIIA and IIIB (N2 disease only) OR have NSCLC Stage IIA-IIIA, IIIB (N2 disease only) and are candidates for complete resection surgery
- Cisplatin-based chemotherapy is mandatory for all subjects (Exception: In subjects with stage IIA disease with no nodal involvement, cisplatin-based chemotherapy can be administered if recommended by the treating physician). When required, a minimum of two cycles of cisplatin-based chemotherapy is mandatory, after which additional therapies can be given based upon local clinical practice and/or guidelines. Typically, chemotherapy is initiated within 60 days of surgery.
- Must have recovered from all toxicities related to prior systemic therapy to grade =< 1 (CTCAE v 4.03). Exception to this criterion: subjects with any grade of alopecia and grade 2 or less neuropathy are allowed to enter the study
- Have ECOG performance status (PS) of 0 or 1

- Have unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery
- Have received any neoadjuvant therapy
- Presence or history of a malignant disease, other than the resected NSCLC, that has been diagnosed and/or required therapy within the past 3 years Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, completely resected carcinoma in situ of any type and hormonal maintenance for breast and prostate cancer > 3 years.
- Have a history of current diagnosis of cardiac disease
- Have uncontrolled diabetes
- Have known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results)
- Subjects must be evaluated for tuberculosis as per local treatment guidelines or clinical practice. Subjects with active tuberculosis are not eligible.
- Have suspected or proven immunocompromised state as described in the protocol
- Had Live and attenuated vaccination within 3 months prior to first dose of study drug (e.g. MMR, Yellow Fever, Rotavirus, Smallpox, etc.).

Both

Non-Small Cell Lung Cancer

Canakinumab (ACZ885)
Canakinumab will be administered periodically for approximately 54 weeks.

Placebo
Placebo will be administered periodically for approximately 54 weeks.

Disease free survival (DFS) by local investigator
DFS is the time from the date of randomization to the date of the first documented NSCLC disease recurrence as assessed by local investigator radiologically or death due to any cause.

July. 03, 2018