Brief Title: 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 Acronym: CANOPY-A (Canopy-A)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Canakinumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03447769

CACZ885T2301

2017-004011-39 (EudraCT Number)

Details and patient eligibility

About

The primary purpose of the study was to compare the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult subjects with stages II -IIIA according to the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) and the subset of IIIB (T>5cm N2 disease) completely resected (R0) non-small cell lung cancer (NSCLC).

Full description

This was a phase III, multicenter, randomized, double-blind study to evaluate the efficacy and safety of canakinumab as adjuvant therapy in adult patients with stages AJCC/UICC v.8 II-IIIA and IIIB (T>5 cm N2) completely resected (R0) NSCLC.

Approximately 1500 patients were planned to be randomized 1:1 to canakinumab, 200 mg subcutaneously (s.c.) every 3 weeks or matching placebo s.c. every 3 weeks. Patients were planned to continue their assigned treatment until they completed 18 cycles (cycle= 21 days) or experienced any one of the following: non-small cell lung cancer (NSCLC) disease recurrence as determined by Investigator; unacceptable toxicity that precluded further treatment; treatment discontinuation at the discretion of the Investigator or patient; start of a new antineoplastic therapy; death, or loss to follow-up, whichever occurred first. All patients who discontinued from the study treatment were to be followed up every 12 weeks for survival until the final OS analysis or death, loss to follow-up or withdrawal of consent for survival follow-up.

Enrollment: 1,382 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Had completely resected (R0) NSCLC AJCC/UICC v. 8 stage IIA-IIIA and IIIB (N2 disease only) OR had NSCLC Stage IIA-IIIA, IIIB (N2 disease only) and were candidates for complete resection surgery.
• Cisplatin-based chemotherapy was mandatory for all subjects (Exception: In subjects with stage IIA disease with no nodal involvement, cisplatin-based chemotherapy could be administered if recommended by the treating physician). When required, a minimum of two cycles of cisplatin-based chemotherapy was mandatory, after which additional therapies could be given based upon local clinical practice and/or guidelines. Typically, chemotherapy was initiated within 60 days of surgery.
• Radiation therapy was allowed if indicated as per local guidelines or practice.
• Had recovered from all toxicities related to prior systemic therapy to grade ≤ 1 (CTCAE v 5.0). Exception to this criterion: subjects with any grade of alopecia and grade 2 or less neuropathy were allowed to enter the study
• Had ECOG performance status (PS) of 0 or 1

Key Exclusion Criteria:

• Had unresectable or metastatic disease, positive microscopic margins on the pathology report, and/or gross disease remaining at the time of surgery
• Had received any neoadjuvant therapy
• Had presence or history of a malignant disease, other than the resected NSCLC, that had been diagnosed and/or required therapy within the past 3 years Exceptions to this exclusion included 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.
• Had a history of current diagnosis of cardiac disease
• Had uncontrolled diabetes
• Had known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (positive or indeterminate central laboratory results)
• Subjects had to be evaluated for tuberculosis as per local treatment guidelines or clinical practice. Subjects with active tuberculosis were not eligible.
• Had 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.).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,382 participants in 2 patient groups, including a placebo group

canakinumab

Experimental group

Description:

Participants received 200mg of canakinumab subcutaneously every 3 weeks for up to 18 cycles (approximately 54 weeks)

Treatment:

Drug: Canakinumab

Placebo

Placebo Comparator group

Description:

Participants received canakinumab placebo subcutaneously every 3 weeks for up to 18 cycles (approximately 54 weeks)

Treatment:

Drug: Placebo