A phase 1 study of intravenous mitazalimab, a CD40 agonistic monoclonal antibody, in patients with advanced solid tumors

Mitazalimab is an agonistic human monoclonal antibody targeting CD40, a target for anti-tumor immunotherapy. This phase 1, dose-escalation study evaluated the safety, dose-limiting toxicities (DLTs), pharmacokinetic and pharmacodynamic profile of mitazalimab. Adults with advanced solid malignancies received mitazalimab intravenously once every-2-weeks. Dose-escalation was pursued with and without pre-infusion corticosteroids for mitigation of infusion-related reactions (IRRs). In all, 95 patients were enrolled in 7 cohorts (n = 50, 75-2000 mu g/kg) with corticosteroids and in 5 cohorts (n = 45, 75-1200 mu g/kg) without corticosteroids. Two patients experienced DLTs (transient Grade-3 headache; Grade-3 drug-induced liver injury [Hy's law]). The most frequently reported (>= 25%) treatment-emergent adverse events were fatigue (44.2%), pyrexia (38.9%), pruritus (38.9%), chills (27.4%), and headache (26.3%). IRRs were reported in 51.6% of patients; pruritus (30.5%; with corticosteroids [36.0%], without corticosteroids [24.4%]) was the most frequent. Following the first infusions of 600 mu g/kg and 2000 mu g/kg, mitazalimab was rapidly cleared from the systemic circulation with mean terminal half-life of 11.9 and 24.1 h, respectively. Pharmacokinetics appeared to exhibit target-mediated drug disposition at the tested doses. Mitazalimab treatment induced higher levels of selected chemokines and transient reduction of B-cells, T-cells, and NK cells. One patient (renal cell carcinoma) displayed partial response lasting 5.6 months. Stable disease was reported by 35 (36.8%) patients, persisting for >= 6 months in 9 patients. Mitazalimab has a manageable safety profile with acceptable pharmacokinetic and pharmacodynamic properties. Future clinical development will evaluate combination with existing treatment options.

Automated summary

Mitazalimab, a human monoclonal antibody targeting CD40, was evaluated in this study for anti-tumor immunotherapy. The results demonstrated its manageable safety profile and pharmacokinetic/pharmacodynamic properties, suggesting its potential as a treatment option for solid malignancies.