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Phase 1, multicenter, open-label study of single-agent bispecific antibody T-cell engager GBR 1342 in relapsed/refractory multiple myeloma.

2018; Lippincott Williams & Wilkins; Volume: 36; Issue: 5_suppl Linguagem: Inglês

10.1200/jco.2018.36.5_suppl.tps81

1527-7755

Joshua Richter, Martin Wermke, John Kauh, Jonathan Back, Yacine Salhi, Venkateshwar A. Reddy, Eliel Bayever, Ola Landgren,

CAR-T cell therapy research

TPS81 Background: Available therapies have improved outcomes in multiple myeloma but patients eventually relapse, requiring treatment with agents that are active in refractory disease. CD38, a transmembrane glycoprotein, is upregulated on myeloma cells and is a validated disease target, evidenced by the anti-myeloma activity of daratumumab, an anti-CD38 human IgG1κ monoclonal antibody. GBR 1342 is a CD3xCD38 bispecific antibody engineered (using Glenmark’s BEAT ® platform) to direct T-cells to CD38-expressing myeloma cells. In preclinical studies, GBR 1342 redirected the cytotoxic potential of T-cells to human myeloma cell lines in vitro and in mouse xenograft models. This ongoing, 2-part, first-in-human study aims to: (1) evaluate the safety profile and maximum tolerable dose (MTD) of GBR 1342 monotherapy in subjects with relapsed/refractory multiple myeloma ( > 3 prior therapies); and (2) further elucidate the safety, tolerability, and preliminary clinical activity of GBR 1342 at the MTD. The study is also evaluating the mechanisms by which GBR 1342 redirects T-cells to tumor and enhances cytolytic activity of cytotoxic T-cells. Methods: In Part 1, intravenous GBR 1342 is administered on Day 1 and Day 15 in 28-day treatment cycles at escalating dose levels (Table). The first 4 cohorts consist of a single subject. Subsequent cohorts will enroll using a 3+3 design. In Part 2, 65 evaluable subjects will be treated at the MTD identified in Part 1 until disease progression or unacceptable toxicity occurs. Primary endpoints include frequency and severity of AEs, number of dose-limiting toxicities during Cycle 1 (Part 1 only), and objective response to GBR 1342 (Part 2 only). Secondary endpoints include pharmacokinetics and anti-tumor activity of GBR 1342 (objective response, progression-free and overall survival). [Table: see text]