A phase Ib/II, multicenter, open-label study of DSP-7888 dosing emulsion in combination with immune checkpoint inhibitors (CPI) nivolumab or pembrolizumab in adult patients (pts) with advanced solid tumors, including platinum-resistant ovarian cancer (PROC).

Abstract

TPS6099 Background: DSP-7888 is a therapeutic cancer vaccine composed of two synthetic peptides derived from Wilms’ tumor 1 (WT1) to promote both cytotoxic and helper T-lymphocyte-mediated immune responses against WT1-expressing tumors. WT1 is overexpressed in various solid tumors, including ovarian cancer. Combining cancer vaccines like DSP-7888 with a CPI may reduce resistance to immunomodulators and improve clinical benefit. A phase Ib/II study is being conducted to evaluate DSP-7888 in combination with a CPI in pts with advanced solid tumors, including PROC (NCT03311334). Methods: This phase Ib/II, open-label, multicenter, two-part dose-search/dose-expansion study investigates DSP-7888 + nivolumab or pembrolizumab in pts with advanced solid tumors (phase Ib), including PROC (phase II). The phase Ib primary objectives are safety, tolerability, and identification of the recommended phase II dose (RP2D). The phase II primary objective is evaluation of objective response rate (ORR); secondary objectives are clinical activity, safety, and tolerability. Pts aged ≥18 years with unresectable, metastatic cancer approved for treatment with nivolumab (phase Ib, Arm 1, n=6–12, 7 enrolled) or pembrolizumab (phase Ib, Arm 2, n=6–12, 6 enrolled), or with PROC (phase II) are eligible. Phase II will enroll ~40 pts into two groups based on programmed death-ligand 1 status (combined positive score of ≥10 [Group 1] or <10 [Group 2]). Clinical activity will be assessed continuously using Bayesian analysis and actual enrollment may increase by ~20 pts/group based on this analysis. Pts in phase II will receive DSP-7888 intradermally (RP2D from phase Ib) once a week (wk) for 6 wks in the induction phase then every 3 wks in the maintenance phase. Beginning Day 1, pembrolizumab will be administered intravenously every 3 wks. In phase II, objective disease will be assessed every 6 wks for 24 wks, then every 12 wks until progression. Endpoints include ORR (per RECIST v1.1) (primary), duration of response, disease control rate (DCR), progression-free survival (PFS), 6-month PFS rate (per RECIST v1.1), and overall survival, immune (i)ORR, iDCR, and iPFS (per iRECIST) (secondary). Exploratory endpoints include blood and tumor tissue biomarkers. Safety and tolerability, assessed by adverse events, will be evaluated throughout the duration of the study and follow-up. This study is currently recruiting patients. Clinical trial information: NCT03311334.