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.

Abstract

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 cancer, endometrial cancer, cervical cancer, ovarian cancer, or non-small-cell lung cancer; and progression on, intolerance to, or ineligibility for local standard-of-care anticancer therapies. Additional criteria include ≥1 measurable lesion and ECOG performance status 0–1. As part of a standard 3+3 dose-escalation design, CR-001 is planned to be administered at 4 dose levels as an intravenous infusion every 2 or 3 weeks. Tumor-specific backfill cohorts will enroll concurrently with dose escalation. Earlier-line participants, including those untreated in the advanced or metastatic setting, may also be eligible to participate in backfill cohorts. The recommended phase 2 dose will be determined based on review of pharmacokinetics/pharmacodynamics, safety, tolerability, and preliminary signs of antitumor activity. Up to 290 patients are planned to be enrolled across the dose-escalation, tumor-specific backfill, and dose-optimization cohorts. This global trial is currently enrolling. Clinical trial information: NCT07335497 .