AACR 2022 | MEDI5752: First-in-human trial of a novel PD-1 and CTLA-4 bispecific checkpoint inhibitor

Ben Tran, MBBS, FRACP, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia, discusses a Phase I, first-in-human trial (NCT03530397) investigating the tolerability and efficacy of MEDI5752, a novel PD-1 and CTLA-4 bispecific checkpoint inhibitor for advanced solid tumors. 86 patients participated in the trial, which involved both dose-escalation and dose-expansion cohorts. The 2000mg cohort tolerated MEDI5752 reasonably well, with the most common adverse events being rashes, hepatic events and hypothyroidism. Adverse events were much less common in the 1500mg cohort, with significantly lower discontinuation rates and instances of grade 3 and 4 adverse events. Importantly, even lower doses of MEDI5752 (around the 500-700mg dose level) were better tolerated and still able to achieve high levels of anti-tumour activity. For example, doses above 225mg MEDI5752 resulted in sustained peripheral PD-1 receptor occupancy of greater than 90%. Additionally, at the 500mg dose level, MEDI5752 was able to achieve a similar peripheral T-cell proliferation to tremelimumab at the intolerable dose of 10mg/kg. Also, the dose-dependent increase in expanded T-Cell clones reached a plateau at 500mg of METI5752. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2022 in New Orleans, LA.