A phase I, first-in-human, open-label, dose escalation and expansion study of PT886 in adult patients with advanced gastric, gastroesophageal junction, and pancreatic adenocarcinomas.

• DOI: 10.1200/jco.2023.41.4_suppl.tps765
• Publication Date: 2023-01-24T21:05:07Z
• Authors: Michael J. Overman; Ramzi Melhem; Mariela A. Blum-M...; Claudia Ramos; Lina Petrosyan; Jack Li; Jessica K Perer; Hui Zou; Ming Wang; Harold M Wright
• Keywords: CD47; Immunoglobulin superfamily; Tolerability

TPS765 Background: PT886 is a novel bispecific antibody that targets Claudin 18.2 (CLDN18.2) and CD47. CLDN18.2 overexpressed in significant proportion of gastric pancreatic adenocarcinomas its restricted expression makes it promising therapeutic target for the treatment these carcinomas. Moreover, studies have found immunoglobulin superfamily CD47 widely across tumor types, plays an important role suppressing phagocytes activity through binding to transmembrane protein SIRPα phagocytic cells. Hence, by targeting both pathways, one can direct macrophage-mediated phagocytotic cells blocking “don’t eat me” signal mediated CD47/ interaction, potentially offering better safety profile than anti-CD47 monoclonal antibodies. Additionally, utilizes IgG1 enhance antibody-dependent cellular cytotoxicity (ADCC) NK phagocytosis (ADCP) macrophages thus increases antitumor activity. The combined cancer killing effects above mechanisms therefore represent approach treating CLDN18.2-positive malignancies. Methods: This open label, Phase I study evaluate safety, tolerability, pharmacokinetics (PK) preliminary efficacy subjects with unresectable or metastatic adenocarcinoma, gastroesophageal junction ductal adenocarcinoma (PDAC) which there no available standard therapy. Approximately 34-58 patients will be enrolled. consists 2 parts: Dose Escalation, Expansion. dose escalation guided 3+3 design determine maximum tolerated (MTD) and/or optimal biological doses expansion. MTD lower level further evaluated expansion cohort recommended phase II (RP2D). Each enrolled patient receive as monotherapy (0.1, 0.3, 1, 3 6 mg/kg QW) intravenous infusion continuously (over 60 minutes) 28-day cycles. primary endpoints are Limiting Toxicity (DLT) MTD, if reached, RP2D single agent. PD markers measured, including T-cell receptor sequencing on circulating T cells, activation studies, serum cytokines assessing tissues. PT886, was recently granted orphan drug designation FDA cancer, has potential new option whose current care limited. Preliminary data anticipated second quarter 2023. Clinical trial information: NCT02178241 .