Safety and Preliminary Efficacy of MBS8(1V270) in Cancer Patients With Advanced Solid Tumours

This is a prospective, open-label, two arms, multinational, multicenter Phase I trial in subjects with advanced solid tumors. The trial consists of two stages: Stage I is a dose escalation stage which will include up to eight cohorts with escalating doses of MBS8(1V270) to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Stage II is an expansion phase in which safety and tolerability of MBS8(1V270) will be assessed at the recommended phase 2 dose established in Stage I of the trial. Stage II comprices two cohorts: One cohort in which MBS8(1V270) will be evaluated in combination with pembrolizumab (Keytruda) in cutaneous melanoma patients with acquired resistance to PD-1 therapy; and one cohort in which MBS8(1V270) will be evaluated as monotherapy in uveal melanoma patients previously treated with T-cell engagers. The dose-escalation in stage 1 is based on the 1+2 design for the first cohort and on the 3+3 design for the following cohorts. The investigational medicinal product is a TLR7 agonist and will be administered intravenously by infusion. Subjects will be treated in cycles. Plasma cytokine levels will be assessed, and tumor biopsies will be taken and evaluated. Radiological tumor assessment by MRI or CT will be performed. Safety will be evaluated by the incidence of adverse events (AEs), serious adverse events (SAEs), DLTs, and use of concomitant medications. Anti-tumor activity of MBS8(1V270) will be evaluated via imaging using RECIST and iRECIST criteria, with iRECIST being the leading tumor evaluation criteria.