Compression therapy of both hands is safely applicable for the prevention of oxaliplatin-induced neuropathy

Abstract

and elevated high-sensitivity C-reactive protein (hs-CRP) in the CANTOS study (Ridker et al 2017). Gevokizumab is a high-affinity recombinant mAb that inhibits IL-1b which was previously explored mainly in inflammatory disorders. Preclinical (Carmi Y et al 2013) and clinical (Isambert N et al 2018) studies have demonstrated that dual blockade of IL-1b and vascular endothelial growth factor (VEGF) may decrease angiogenesis and modulate the immune response in the tumor microenvironment resulting in decreased tumor size providing a rationale for combining gevokizumab with established anti-angiogenic agents. Methods: This is a multi-cohort, open-label, multi-center, phase Ib study (NCT03798626) to determine the pharmacodynamically-active dose (PAD) of gevokizumab along with tolerable dose and preliminary efficacy of gevokizumab in combination with the standard of care (SOC) anticancer therapies in patients with 1 st and 2 nd line mCRC, 2 nd line mGEC, and 2 nd /3 rd line mRCC. Key inclusion criteria: !1 measurable lesion, ECOG PS 0-1 and adequate bone marrow and organ functions. Key exclusion criteria: previous treatment with gevokizumab or other IL-1b/IL-6 inhibitors or any of the study drugs, symptomatic brain metastases, significant bleeding risk, uncontrolled cardiovascular disease and prohibited medications per protocol or contraindicated to the SOC regimen. The study will be conducted in part 1 [PAD determination part (1a) and safety run-in (1b) to determine the recommended dose for expansion (RDE)] and part 2 (expansion). In part 1a, patients in cohort A (1 st line mCRC, hs-CRP ! 10mg/L, $30 patients) and cohort B (2 nd line mCRC, hs-CRP ! 10mg/L, $30 patients) will be randomized 1:1:1 to receive gevokizumab 30/60/120 mg IV monotherapy for two weeks. 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 þ 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)þramucirumabþpaclitaxel, and gevokizumab (PAD)þcabozantinib, respectively. The primary objectives of part 1 include determination of PAD of gevokizumab in mCRC patients as measured by hs-CRP change from baseline (part 1a, cohorts A and B) and establishing the RDE of the regimen (part 1b, all cohorts). In part 2, patients of all cohorts will receive gevokizumab (RDE) along with SOC therapy. Cohorts A and B will include $ 40 patients (20 patients each with hs-CRP ! 10mg/L and hs-CRP < 10mg/L). Cohorts C and D will include $20 patients each with hs-CRP ! 10mg/L. 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, and immunogenicity. P À 285 The role of active nutritional intervention in patients receiving c...