American Association for Cancer Research
10780432ccr200452-sup-236897_2_supp_6460361_qy8jyd.docx (12.79 kB)

Supplementary Table 1 from Safety and Clinical Activity of MEDI1873, a Novel GITR Agonist, in Advanced Solid Tumors

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journal contribution
posted on 2023-03-31, 22:00 authored by Ani S. Balmanoukian, Jeffrey R. Infante, Raid Aljumaily, Aung Naing, Ashish V. Chintakuntlawar, Naiyer A. Rizvi, Helen J. Ross, Michael Gordon, Philip R. Mallinder, Nairouz Elgeioushi, Ignacio González-García, Nathan Standifer, Jennifer Cann, Nicholas Durham, Shahram Rahimian, Rakesh Kumar, Crystal S. Denlinger

Supplementary Table 1. Characteristics of patients with prolonged SD ({greater than or equal to}24 weeks)



The safety and preliminary efficacy of MEDI1873, an agonistic IgG1 fusion protein targeting glucocorticoid-induced TNF receptor–related protein (GITR), were evaluated in an open-label, first-in-human, phase I, dose escalation study in previously treated patients with advanced solid tumors. Two single-patient cohorts at 1.5 and 3 mg i.v. were followed by 3+3 dose escalation in six cohorts at 7.5, 25, 75, 250, 500, and 750 mg, all every 2 weeks, for up to 52 weeks. Primary endpoints were safety and tolerability, dose-limiting toxicities (DLT), and MTD. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. Forty patients received MEDI1873. Three experienced DLTs: grade 3 worsening tumor pain (250 mg); grade 3 nausea, vomiting, and headache (500 mg); and grade 3 non-ST segment elevation myocardial infarction (750 mg). An MTD was not reached and treatment was well tolerated up to 500 mg. Most common treatment-related adverse events were headache (25%), infusion-related reaction (17.5%), and decreased appetite (17.5%). MEDI1873 exposure was dose proportional. Antidrug–antibody incidence was low. MEDI1873 increased peripheral CD4+ effector memory T-cell proliferation as well as cytokines associated with effector T-cell activation at dose levels ≥75 mg. The best response was stable disease (SD) in 17 patients (42.5%), including 1 unconfirmed partial response. Eight patients (20.0%) had SD ≥24 weeks. MEDI1873 showed acceptable safety up to 500 mg i.v. every 2 weeks with pharmacodynamics activity, and prolonged SD in some patients. However, further development is not planned because of lack of demonstrated tumor response.

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