Clin cancer res: The results of the first clinical trial of the anti-tumor necrotic necrotogenic sub-antibody MK-4166 for the treatment of advanced solid tumors

Immuno checkpoint inhibitors (ICI) targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) or programmed death subject 1/programmed death ligation 1 improved prognostication in a wide range of cancer patients, but a significant proportion of patients remained unresponsive to ICI therapy.
In this first Phase 1 trial in humans (NCT02132754), researchers explored the application of the humanized IgG1 astigger monoclonal antibody MK-4166, which targets GITR, in advanced solid tumors.
the study was divided into two queues, dose/proof queues or extended queues; dose incremental queues recruited patients with metastasis solid tumors, only MK-4166 (0.0015-900mg) or combined Pym monoantigens (200mg); and extended queues recruited patients with advanced melanoma.
the main purpose is to identify the maximum to-dosage of MK-4166 and to assess its safety and tolerance.
end points include objective mitigation rate (ORR) and T-cell T-cell inflammatory gene expression spectrum (GEP) analysis.
recruited a total of 113 patients (48 single-drug treatment, 65 combined treatment; 20 expanded queues).
46 patients (40.7%) had ≥3 adverse events, 9 of which (8.0%) were related to treatment.
no treatment-related deaths were observed.
dose-limiting toxicity event (bladder perforation) in the single drug group is thought to be associated with the study of the drug.
the serum concentration of A: MK-4166;
of MK-4166 showed that GITR was less used in circulating T cells as the dose increased.
A: Tumor size changes in extended cohort patients; B:ICI initial treatment patients' response and duration in dose incremental cohorts (n-45), the combined treatment group had a period of objective remission (ORR 2.2%).
in the extended queue, 8 out of 13 patients with melanoma with ICI initial treatment were relieved (ORR 62%; 95% CI 32% to 86%; 5 cases of complete remission and 3 cases of partial remission).
seven patients who had been pre-treated with ICI did not respond.
regardless of THEP status, ICI patients with primary treatment had a higher response rate.
, the tolerance of MK-4166 (900mg) or combined Pym monoantigen therapy in patients with advanced solid tumors is within acceptable range.
mainly in patients with melanoma who benefit from combined therapy.
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