Abstract CT135: Preliminary safety and efficacy of DSP-7888 plus nivolumab (NIV) or pembrolizumab (PEM) in patients (pts) with advanced solid tumors (ASTs): A phase (Ph) 1b/2 open-label study
Authors: Harb Wael A. , Origuchi Makoto , Cobb Patrick W. , Wise-Draper Trisha , Suginobe Natsuko , Nakamura Megumi , Goto Masashi , Chen Aaron , Li Jian , Wade James 
Published: June 2022

Abstract
Background: DSP-7888—an investigational immunotherapeutic cancer vaccine derived from Wilms’ tumor 1 (WT1)—induced WT1-reactive T cells, the activity of which was maintained and enhanced by anti-PD-1 mAbs (preclinical; Goto, et al. ASH 2016). Results from the Ph 1b dose search cohort of a Ph 1b/2 study of DSP-7888 + immune checkpoint inhibitors (ICIs) NIV or PEM in ASTs (NCT03311334) are presented.
Methods: Pts (aged ≥18 y; ECOG PS 0-1; locally advanced/metastatic solid tumors; approved for NIV or PEM) received intradermal (ID) DSP-7888 10.5 mg once weekly (wk) (Q1W) + NIV 240 mg IV Q2W for 4 (Arm 1) or PEM 200 mg IV Q3W for 6 (Arm 2) wks (induction), then DSP-7888 + NIV (Q2W; Arm 1) or PEM (Q3W; Arm 2) (maintenance). A DSP-7888 3.5-mg dose cohort would open if dose limiting toxicities (DLTs) occured in &gt;1 of 6 pts. Primary objectives: evaluate safety (including DLTs) and identify the recommended Ph 2 dose of DSP-7888 + NIV or PEM.
Results: At data cutoff (March 30, 2021), 13 pts (mean age 63.8 [range 38-82] y; 61.5% male; median 3 (1-5) lines of prior therapy; 84.6% prior ICIs) were enrolled and treated with DSP-7888 10.5 mg + NIV (Arm 1, n=7) or PEM (Arm 2, n=6). Treatment-emergent adverse events (TEAEs) were reported in 100% (any grade) and 76.9% (grade ≥3; most commonly injection site reactions [ISR; 30.8%]) of pts (Table). No DLTs occurred during the evaluation period (NIV, 4 wk; PEM, 6 wk), establishing 10.5 mg as the recommended dose for DSP-7888 + NIV or PEM. Serious AEs were reported in 7 (53.8%) pts (2 [15.4%] related to DSP-7888). At efficacy data cutoff (May 4, 2020), 2 (15.4%) pts with prior ICIs achieved partial response, which lasted 9.5 and 5.5+ months; 6 pts achieved stable disease (n=4 ≥8 months) and 3 had progressive disease.
Conclusions: DSP-7888 + NIV or PEM was generally tolerable at 10.5 mg ID (most common TEAE was ISR) and showed evidence of preliminary antitumor activity. An expansion cohort in ovarian cancer is enrolling.
Table. Safety and Efficacy (N=13a) DSP-7888 + NIV (n=7) DSP-7888 + PEM (n=6) Overall (N=13) Patient characteristics Prior lines of therapy, n (%) -1 0 1 (16.7) 1 (7.7) -2 2 (28.6) 1 (16.7) 3 (23.1) -≥3 5 (71.4) 4 (66.7) 9 (69.2) Prior ICI, n (%) 7 (100) 4 (66.7) 11 (84.6) Safety All patients with TEAE grade ≥3, n (%)b — — 10 (76.9) TEAEs grade ≥3 (in ≥2 patients), n (%)b -Injection site reaction — — 4 (30.8) Pts with treatment-emergent SAEs, any grade, n (%)b — — 7 (53.8) Efficacy ORR (CR+PR), n (%) [95% CI] 2 (28.6) [3.7, 71.0] 0 2 (15.4) [1.9, 45.5] Best overall response, n (%) -PRc 2 (28.6) 0 2 (16.7) -SD 3 (42.9) 3 (50.0) 6 (46.2) -PD 0 3 (50.0) 3 (23.1) -Non-CR/Non-PD 1 (14.3) 0 1 (7.7) -NE 1 (14.3) 0 1 (7.7) Disease control rate (CR+PR+SD+Non-CR/Non-PD), n (%) [95% CI] 6 (85.7) [42.1, 99.6] 3 (50.0) [11.8, 88.2] 9 (69.2) [38.6, 90.9] aTumor types included non-small cell lung cancer (n=7), urothelial cancer (n=3), gastroesophageal junction adenocarcinoma (n=1), head and neck squamous cell carcinoma (n=1), and renal cell carcinoma (n=1). For inclusion, patients either progressed on their prior treatment or were being treated with NIV or PEM, achieved at least SD, and could benefit from the addition of DSP-7888 (physician’s judgement). bRegardless of causality. cOf the patients that exhibited a PR, 1 had renal cell carcinoma and 1 had urothelial cancer. Both patients were previously treated with an ICI (NIV and atezolizumab, respectively. DOR w as 9.5 and 5.5 (+) months in the patients with renal cell carcinoma and urothelial cancer, respectively (DOR was defined as the time, in months, from the first documentation of CR or PR to the first documentation of PD or death due to any cause. Patients who were alive and progression-free as of the analysis cut-off date were censored (+) at their last date of response assessment. CI, confidence interval; CR, complete response; ICI, immune checkpoint inhibitor; DOR, duration of response; NE, not evaluable; NIV, nivolumab; ORR, overall response rate; PD, progressive disease; PEM, pembrolizumab; PR, partial response; SAE, serious adverse event; SD, stable disease; TEAE, treatment-emergent adverse event.
Citation Format: Wael A. Harb, Makoto Origuchi, Patrick W. Cobb, Trisha Wise-Draper, Natsuko Suginobe, Megumi Nakamura, Masashi Goto, Aaron Chen, Jian Li, James Wade III. Preliminary safety and efficacy of DSP-7888 plus nivolumab (NIV) or pembrolizumab (PEM) in patients (pts) with advanced solid tumors (ASTs): A phase (Ph) 1b/2 open-label study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT135.