gevokizumab (VPM087) / Novartis, Xoma - LARVOL DELTA

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers (clinicaltrials.gov) - P1 | N=167 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRP

Phase Ib study of gevokizumab (GEVO) in combination with standard-of-care (SoC) anticancer therapies in patients (pts) with metastatic colorectal cancer (mCRC), metastatic gastroesophageal cancer (mGEC), and metastatic renal cell cancer (mRCC). (ASCO-GI 2025) - P1 | "The safety and tolerability of GEVO combinations was acceptable. The primary PFS rates did not meet the PoC criteria. Baseline levels of hs-CRP, IL-6 and IL-1β in pts with 2L mCRC, and on-treatment reduction of ctDNA in pts with 1L + 2L mCRC may have prognostic value."

Clinical • Combination therapy • Metastases • P1 data • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CRP • IL1B • IL6

A Meta-Analysis Methodology in Stan to Estimate Population Pharmacokinetic Parameters from Multiple Aggregate Concentration-Time Datasets: Application to Gevokizumab mPBPK Model. (PubMed, Pharmaceutics) - "Conclusively, the proposed method could be applied to monoclonal antibodies for which the second-generation mPBPK model has been proposed as well as to other drugs with different PK models when only a published graph with aggregate concentration-time data is available. In addition, the method could be used when multiple aggregate datasets from different sources need to be combined in a meta-analysis approach in order to estimate the PopPK parameters of a drug."

Journal • PK/PD data • Retrospective data • IL1B

Identification of critical genes and metabolic pathways in rheumatoid arthritis and osteoporosis toward drug repurposing. (PubMed, Comput Biol Med) - "The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Osteoporosis • Rheumatoid Arthritis • Rheumatology • CCL2 • HIF1A • IL10 • IL1B • IL6 • MMP9 • STAT3 • TGFB1 • TP53

Targeted anti-IL-1β Bacteroides fragilis outer membrane vesicles alleviate inflammatory injury in diabetic nephropathy (ERA-EDTA 2024) - " We recombinantly expressed the scFv based on the Gevokizumab sequence in Escherichia coli, and loaded it into the OMVs derived from Bacteroides fragilis by multiple ultrasounds... Our findings demonstrated that OMVs of Bacteroides fragilis targeting the kidney can deliver the IL-1β scFv to the renal tubulointerstitium and reduce the renal interstitial injury in DN by antagonizing local inflammation."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Inflammation • Nephrology • Renal Disease • IL1B

Efficacy and safety of envafolimab in the treatment of advanced dMMR/MSI‑H solid tumors: A single‑arm meta‑analysis. (PubMed, Oncol Lett) - "Most of the adverse reactions were mild and the rate of 3/4 grade TEAE was 10.37% (95% CI, 6.14-14.60%). Gevokizumab was effective and safe in the treatment of patients with advanced dMMR/MSI-H solid tumors and its convenience could significantly improve patient compliance; therefore, the clinical application of envafolimab is promising."

Journal • Metastases • Retrospective data • Microsatellite Instability • Oncology • Solid Tumor • MSI

ADH1B, ADH1B/C and CYP2E1 Gene Polymorphism and the Risk of Fetal Alcohol Spectrum Disorder. (PubMed, Genes (Basel)) - "In the present study, we considered three polymorphisms of genes implicated in the synthesis of enzymes involved in ethanol metabolism, i.e., ADH1b (rs1229984), ADH1b/c (rs1789891), and CYP2E1 (rs3813867)...There were no statistically significant differences between the respective groups of genotypes of the studied polymorphisms. However, the genetic background of FASD is still elusive."

Journal • Addiction (Opioid and Alcohol) • ADH1B • CYP2E1

NSABP FC-12: A single-arm, phase II study to evaluate treatment with gevokizumab in patients with stage II/III colon cancer who remain ctDNA+ after curative surgery and adjuvant chemotherapy. (ASCO 2022) - "If ≥9 of 31 pts (29%) are alive and recurrence-free at 12 mos, then gevokizumab will be considered promising for further study. Enrollment continues towards the primary endpoint."

Circulating tumor DNA • Clinical • P2 data • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IL1B • TMB

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers (clinicaltrials.gov) - P1 | N=168 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2025 ➔ Oct 2024

Trial completion date • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRP

Targeting the IL-1β pathway for cancer immunotherapy remodels the tumor microenvironment and enhances antitumor immune responses. (PubMed, Cancer Immunol Res) - "Here, the effects of IL-1β blockade induced by the monoclonal antibodies canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-PD-1, anti-VEGFα and anti-TGFβ treatment in syngeneic and humanized mouse models of cancers of different origin. Overall, the results presented here support the potential use of IL-1β inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages and lines of treatment."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Oncology • CAFs • IL1B • TGFB1

". @Novartis trims pipeline as it prepares for spin-off of generics unit @Sandoz, with cull including anti-IL-1 sold tumour candidate VPM087 https://t.co/i2rDdjr5X5" (@pharmaphorum)

Oncology

Targeting IL-1&[beta] pathway for cancer immunotherapy (AACR-NCI-EORTC 2019) - "Anti-mouse IL-1β blocking antibody was used to evaluate efficacy in murine syngeneic models of breast (4T1) and lung (LL-2) cancer either as a single agent or in combination with PD-1 inhibitor and docetaxel...In the humanized H358 NSCLC mouse model, the combination of canakinumab and the anti-PD-1 monoclonal antibody, pembrolizumab, significantly slowed tumor growth by more than 50% vs control antibodies...Conclusion Our results highlight the role for IL-1β in tumor immunomodulation and that the pathophysiological role of the IL-1β pathway in innate immunity might have important consequences on T cell function and checkpoint blockade in cancer. These results support the ongoing clinical evaluation of IL-1β inhibitors such as canakinumab and gevokizumab and in combination with other therapeutic agents across several cancers."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • IL1B • IL6

[VIRTUAL] Targeting tumor-promoting inflammation (TPI) via the IL-1βpathway for cancer immunotherapy (AACR-II 2020) - "Selective IL-1β inhibitors like canakinumab (CAN) and gevokizumab (GEV) aim to target TPI within the tumor microenvironment (TME) by reducing tumor-associated immune suppression...We have utilized preclinical models to gain further insights into the mechanistic role of CAN and GEV in cancer development and progression. Preclinical efficacy of anti-human IL-1β antibodies, CAN and GEV was assessed using humanized mouse models of non-small cell lung cancer (NSCLC, H358), triple-negative breast cancer (TNBC, MDA-MB-231) and colorectal cancer (CRC, SW480) either as single agents or in combination with other immunomodulatory agents including PD-1 inhibitor pembrolizumab (PEM) and anti-VEGF therapy. A murine surrogate IL-1β blocking antibody clone 01BSUR was used to evaluate efficacy in murine syngeneic models of breast (4T1) and lung (LL-2) cancer either as single agent or with PD-1 inhibitor and docetaxel (DOC)... These data provide key insights into the biology behind IL-1β..."

Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer • IL1B • IL6

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers (clinicaltrials.gov) - P1 | N=167 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRP

NSABP FC-12: A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: NSABP Foundation Inc | N=31 ➔ 0 | Recruiting ➔ Withdrawn

Circulating tumor DNA • Enrollment change • Trial withdrawal • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Systematic Review of Safety and Efficacy of IL-1-Targeted Biologics in Treating Immune-Mediated Disorders. (PubMed, Front Immunol) - "This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547."

Review • Cardiovascular • Dermatology • Diabetes • Genetic Disorders • Gout • Graft versus Host Disease • Hidradenitis Suppurativa • Idiopathic Arthritis • Immunology • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Rare Diseases • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Type 1 Diabetes Mellitus • Uveitis

NSABP FC-12: A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy (clinicaltrials.gov) - P2 | N=31 | Recruiting | Sponsor: NSABP Foundation Inc | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2026 ➔ Feb 2027 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Circulating tumor DNA • Enrollment open • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers (clinicaltrials.gov) - P1 | N=172 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2025 ➔ Jan 2025 | Trial primary completion date: Nov 2023 ➔ Jan 2023

Combination therapy • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRP

NSABP FC-12: A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: NSABP Foundation Inc | Trial completion date: Nov 2025 ➔ Feb 2026 | Trial primary completion date: Nov 2024 ➔ Feb 2025

Circulating tumor DNA • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Current treatment options for monogenic periodic fever syndromes - the role of interleukin 1 inhibitors. (PubMed, Cas Lek Cesk) - "The most available are anakinra, canakinumab and rilonacept. Moreover, several clinical trials are currently underway with other very promising drugs, such as gevokizumab, tadekinig alfa or tranilast. In the following review, we provide a new perspective on the efficacy and safety of IL-1 inhibitors that have provided the novel results coming from recently published clinical trials."

Journal • Cardiovascular • Genetic Disorders • Inflammation • Oncology • TNFA

A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy (clinicaltrials.gov) - P2; N=31; Not yet recruiting; Sponsor: NSABP Foundation Inc

Circulating tumor DNA • Clinical • New P2 trial • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MRI

Gevokizumab, an interleukin-1β (IL-1β) monoclonal antibody (mAb), in metastatic colorectal cancer (mCRC), metastatic gastroesophageal cancer (mGEC) and metastatic renal cell carcinoma (mRCC): “first-in-cancer” phase Ib study (ESMO-GI 2019) - P1; "...Treatment with anti-IL-1β monoclonal antibody (mAb) canakinumab was associated with a dose-dependent reduction in lung cancer incidence and mortality in patients with atherosclerosis and elevated high-sensitivity C-reactive protein (hs-CRP) in the CANTOS study (Ridker et al 2017)...In part 1b, patients from cohorts A and B will continue to receive gevokizumab Q4W at doses administered in part 1a in combination with SOC [bevacizumab + modified FOLFOX6 (cohort A)/FOLFIRI (cohort B)]. Patients in cohort C (2 nd line mGEC, ∼6 patients) and cohort D (2 nd /3 rd line mRCC, ∼6 patients) will start with gevokizumab (PAD)+ramucirumab+paclitaxel, and gevokizumab (PAD)+cabozantinib, respectively...The primary objective of Part 2 is to determine the preliminary efficacy of the gevokizumab combination as measured by PFS rate. Major secondary objectives include ORR, duration of response, OS, safety, the pharmacokinetics of gevokizumab and other agents in the combination regimens,..."

P1 data • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers (clinicaltrials.gov) - P1; N=172; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Nov 2024 ➔ Apr 2025; Trial primary completion date: Jun 2023 ➔ Oct 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRP • MRI

Rheumatoid Arthritis Associated Episcleritis and Scleritis: An Update on Treatment Perspectives. (PubMed, J Clin Med) - "In refractory cases, treatment with anti TNF biologic agents (infliximab, and adalimumab) is now recommended. Evidence suggests that rituximab may be an effective option, and further studies are needed to investigate the potential role of gevokizumab, tocilizumab, abatacept, tofacitinib, or ACTH gel. A close cooperation is needed between the rheumatology or internal medicine specialist and the ophthalmologist, especially when scleritis may be the first indicator of an underlying rheumatoid vasculitis."

Journal • Review • Immunology • Inflammation • Inflammatory Arthritis • Ocular Inflammation • Ophthalmology • Rheumatoid Arthritis • Rheumatology • Scleritis • Vasculitis

Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers (clinicaltrials.gov) - P1; N=172; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Jul 2024 ➔ Nov 2024; Trial primary completion date: Jan 2023 ➔ Jun 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CRP