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.

Conditions: Non-small Cell Lung Cancer

Summary: the purpose of this study was to evaluate the 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 of pembrolizumab as a single agent and the dynamic of the tumor microenvironment changes on treatment.

this was a randomized, phase ii, open-label study evaluating canakinumab, an anti-il-1β monoclonal antibody, or pembrolizumab, a monoclonal antibody designed to block the pd-1 receptor, as monotherapy or in combination as neoadjuvant therapy. the study population included adult subjects with resectable non-small cell lung cancer (nsclc) planned for surgery in approximately 4-6 weeks. subjects were treated for a maximum duration of 6 weeks (2 cycles) until surgery, progression, unacceptable toxicity or discontinuation from the study treatment for any other reason. subjects were randomized in a 2:2:1 ratio to one of the 3 treatment arms (canakinumab alone or canakinumab in combination with pembrolizumab or pembrolizumab alone). surgery was performed between 4 to 6 weeks after the first dose of study treatment. all randomized subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).

Eligibility 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 have been 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 was required for study enrollment. an archival biopsy was 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. 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 was permitted * subject with suspected or proven immunocompromised state or infections

Keywords: 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