Ilaris (canakinumab)

The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin.

Adult-onset Still's disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays.

P3, N=148, Recruiting, AO GENERIUM | Active, not recruiting --> Recruiting

This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

P2, N=23, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Sponsor Decision

P1/2, N=41, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jun 2024 --> Aug 2025

P2, N=75, Recruiting, Peter Shields | Not yet recruiting --> Recruiting | Initiation date: Sep 2023 --> Mar 2024

P2, N=23, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications.

Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n=10) were treated with canakinumab, a high-affinity monoclonal human anti-interleukin-1β (IL-1β), the PD-1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Within the tumor we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD-1 and IL-1β blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

P3, N=148, Active, not recruiting, AO GENERIUM

P3, N=56, Recruiting, University Hospital, Basel, Switzerland | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

P1, N=105, Completed, AO GENERIUM

P=N/A, N=5000, Recruiting, Duke University | Trial completion date: Jul 2024 --> Sep 2027 | Trial primary completion date: May 2024 --> Sep 2026

This review explores cutting-edge anti-inflammatory interventions, their potential efficacy in preventing and alleviating atherosclerosis, and the role of nanotechnology in delivering drugs more effectively and safely.

P2, N=41, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

In this secondary analysis of specimens from the CANTOS trial, the investigators find that patients with clonal hematopoiesis mutations, particularly in the TET2 gene, predict a benefit of decreased cancer risk with the administration of the anti-IL1β agent canakinumab...Such personalized approaches can potentially enhance the feasibility of cancer prevention trials. See related article by Woo et al., p. XX (2).

No abstract available

P1, N=33, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons

P2, N=10, Terminated, University of Leipzig | It is not considered likely that the CANFIRE trial will be able to reach the target number of patients. Clinical responders will be further treated within the trial (expected duration: 3 years after stop of enrollment).

The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab vs those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL-1β blockade cooperating with CH mutations to modify the disease course.

The phase II CANTOS trial incidentally showed reduced lung cancer incidence and mortality with the IL-1β inhibitor canakinumab... Our study shows promising prognostic value of IL-1β expression in NSCLC, associating low expression with improved OS across NSCLC subtypes. IL-1β expression is closely linked to key driver mutations in NSCLC and may have predictive value for ICIs. The findings suggest the potential benefit of targeting IL-1β in high IL-1β expressing NSCLC with driver mutations.

P2, N=24, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=138 --> 24

P2, N=34, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Terminated by sponsor

This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

P1/2, N=41, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

Overproduction of pro-inflammatory cytokines and the hyperactivation of NOD2-mediated signaling pathways were found in the NOD2 variant Q902K patient with YAOS. NOD2-RIP2-MAPK pathway might play a pivotal role in the pathogenesis of YAOS. These results provide new perspectives for targeted therapies in YAOS.

Data from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.

P1/2, N=41, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1b/2 --> P1/2

Adding canakinumab to docetaxel did not provide additional benefit for patients with advanced NSCLC who had progressed after PDC and immunotherapy.

No abstract available

However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

This study provides one of the largest epidemiologic datasets for CAPS. While early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS following canakinumab treatment.

P2, N=138, Recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2025 --> Jun 2024 | Trial primary completion date: Oct 2025 --> Jun 2024

Cholesterol-inflammation lowering agents (statins), monoclonal antibodies targeting IL-1 and IL-6 (canakinumab and tocilizumab), disease-modifying antirheumatic drugs (methotrexate), sodium-glucose transport protein-2 (SGLT2) inhibitors, colchicine and xanthene oxidase inhibitor (allopurinol) have shown promising results in reducing inflammation, regressing atherogenic plaque and modifying the course of CAD. Here, we review the complex interplay between inflammatory, endothelial, smooth muscle and foam cells. Moreover, the putative role of inflammation in atherosclerotic CAD, underlying mechanisms and potential therapeutic implications are also discussed herein.

Intestinal BD may flare up after surgical treatment and require multiple surgeries. Introducing pharmacotherapy as soon as possible after surgical treatment is important to control the disease.

P3; Trial completion date: Jul 2024 --> Jun 2027

The patient was ultimately treated with canakinumab (Il-1 inhibitor), with near resolution of symptoms. This case demonstrates the importance of a broad differential diagnosis and maintaining a high clinical suspicion for rare diseases when presented with a complex form of an otherwise common condition.

The addition of canakinumab to first-line pembrolizumab and CT did not prolong PFS or OS in patients with NSCLC.

The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs)...Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%)...The treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

P4, N=1000, Recruiting, Jeffrey Curtis | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: May 2023 --> Feb 2024

Additionally, 33% and 56% were refractory to lenalidomide and luspatercept therapy, respectively. The combination of canakinumab and darbepoetin was safe and well tolerated and 300mg of canakinumab is the RP2D. Canakinumab inhibited inflammasome activation as evidenced by a reduction of ASC specks although this did not translate to clinical responses. Phase 2 of the study will focus on patients with lower transfusion burden and molecular subsets with highest IL-1β expression (e.g.