A Phase II Study of Ivonescimab Combined With Intraperitoneal Paclitaxel in Patients With High-Grade Metastatic Appendiceal Adenocarcinoma (AA)
brief summary
To evaluate the safety and effectiveness of Ivonescimab combined with intraperitoneal paclitaxel (IP PTX) in patients with unresectable metastatic high-grade Appendiceal Adenocarcinoma (AA).
detailed description
PRIMARY OBJECTIVES To evaluate the safety and efficacy as measured by the disease control rate (DCR) of Ivonescimab combined with IP PTX in patients with unresectable metastatic high-grade AA
SECONDARY OBJECTIVES:
I. To evaluate progression free survival (PFS) following treatment with ivonescimab and IP PTX in patients with unresectable metastatic high-grade AA.
II. To evaluate overall survival following treatment with ivonescimab and IP PTX in patients with unresectable metastatic high-grade AA.
III. To evaluate the prognostic value of biochemical response including serum tumor markers and correlation with radiographic, pathologic, and clinical response assessment.
IV. To evaluate the prognostic value of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and/or peritoneal fluid tumor DNA.
V. To evaluate pathologic response following treatment with ivonescimab and IP PTX in patients with unresectable metastatic high-grade AA.
VI. To investigate clinical, pathologic, and molecular features associated with therapeutic response to ivonescimab and IP PTX in patients with unresectable high-grade metastatic AA.
VII. To assess rate of initially unresectable metastatic high-grade AA able to undergo cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) after treatment.
VIII. To evaluate combining biochemical, radiographic, and/or pathologic data into a composite surrogate response marker predictive of overall survival (OS).
OUTLINE:
Patients undergo laparoscopy and placement of IP port at least 5 days prior to cycle 1. Patients then receive paclitaxel IP over at least 30 minutes every 2 weeks during cycles 1-5 and ivonescimab intravenously (IV) over 60-120 minutes every 2 weeks during cycles 2, 3, and 4 only. After 5 cycles (at Week 12), patients without disease progression or unacceptable toxicity may receive ivonescimab with or without IP paclitaxel every 2-3 weeks for up to 2 years. Patients also undergo tumor biopsy during screening and computed tomography (CT) or positron emission tomography (PET)/CT, as well as blood sample collection throughout the study.