Adapted Guided Stereotactic Body Radiotherapy Combined With Chemotherapy and Enhancement of Novel Drug Ivonescimab for Pancreatic Cancer (ASCEND)

Summary

This study aims to evaluate the safety and efficacy of Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, in combination with stereotactic body radiotherapy (SBRT) and chemotherapy for treating locally advanced pancreatic cancer (LAPC). The Phase Ib portion is a dose-escalation study to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended Phase II dose (RP2D) of Ivonescimab. The Phase II portion will assess the median progression-free survival (mPFS) of patients receiving Ivonescimab with SBRT (25-50Gy/5F) and modified FOLFIRINOX chemotherapy. The study aims to provide critical insights into treatment options for LAPC and inform future therapeutic strategies.

Timeline

Start

2025-02-08

Primary completion

2028-02-18

Completion

2028-02-18

Publications

• Background Cheng WC, Wang G, Mei Q. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172. doi: 10.1001/jama.2024.23088. No abstract available.
• Background Liu Z, Shan D, Han X. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172-173. doi: 10.1001/jama.2024.23091. No abstract available.
• Background Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X, Dong X, Meng S, Wu F, Hou X, Dai Y, Song W, Li B, Wang ZM, Xia Y, Zhou C. A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23.
• Background Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, Wang ZM, Li B, Xia Y, Coward JIG. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037. doi: 10.1136/jitc-2023-008037.
• Background Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29.
• Background HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Xu F, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Feng J, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Cheng Y, Chen L, Hou X, Zhang Y, Guo J, Wang Z, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhang L. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. 2024 Aug 20;332(7):561-570. doi: 10.1001/jama.2024.10613.

Drugs

Indications