ASCEND: A phase 1/2, dose-escalation, optimization, and dose-expansion study to evaluate the safety and antitumor activity of CR-001 in adults with locally advanced or metastatic solid tumors.

作者：Meredith Pelster, Amita Patnaik, Rebecca Kristeleit, Seung Tae Kim, Emily Putiri, Lindsey Granlund, Paul Herszdorfer, Bradley Sumrow, Ana Oaknin · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.tps2693 · 研究领域：Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research、Angiogenesis and VEGF in Cancer

TPS2693 Background: CR-001 is a tetravalent bispecific antibody targeting anti-programmed cell death-1 (PD-1) and vascular endothelial growth factor (VEGF), designed to enhance antitumor activity through combined immune modulation and antiangiogenic effects. Its proposed mechanism of action involves dual binding and blockade of both PD-1/programmed death ligand-1 (PD-L1) and VEGF/vascular endothelial growth factor receptor 2 (VEGFR2) signaling. The blockade of VEGF signaling is aimed at inhibiting tumor angiogenesis and reversing immunosuppressive effects in the tumor microenvironment, while PD-1 binding is aimed at preventing T-cell suppression, thereby promoting the immune recognition and elimination of tumor cells. The established benefit/risk profiles and regulatory precedents for PD-1-, VEGF-, and dual-pathway-directed antibodies support evaluation of CR-001 in solid tumors. Methods: ASCEND (NCT07335497) is a global, first-in-human, open-label, phase 1/2 study assessing CR-001 monotherapy in adults with advanced solid tumors. The purpose of this study is to determine the safety and tolerability of CR-001 and identify the maximum tolerated dose, and/or recommended phase 2 dose. The study will initially involve three parts: dose escalation, backfill, and dose optimization. Key eligibility criteria include: age ≥18 years; locally advanced (nonresectable) or metastatic hepatocellular carcinoma, biliary tract cancer, gastric or gastroesophageal junction cancer, colorectal can...