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.
Pathologically or cytologically confirmed unresectable LAPC, as defined by the 8th edition of the American Joint Committee on Cancer (AJCC);
Age between 18 and 80 years;
At least one measurable pancreatic cancer lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
History of any malignant tumors within the past 5 years, except for cured localized tumors;
Uncontrolled infections (e.g., active tuberculosis or hepatitis), uncontrolled systemic diseases, poorly controlled hypertension or diabetes, or severe comorbidities within the past six months, including myocardial infarction, cerebral embolism, or significant arrhythmias;
Previous treatment with drugs targeting other stimulatory or co-inhibitory T-cell receptors;
Prior radiotherapy within 2 weeks before enrollment;
Single group
Ivonescimab
Drug1. Phase Ib (Dose Escalation): In this phase, patients will receive Ivonescimab in escalating doses, with the aim of determining the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended Phase II dose (RP2D). The dose-escalation process will follow a 3+3 design over a 4-week period to establish the RP2D of Ivonescimab. 2. Phase II (Efficacy Evaluation): After establishing the RP2D, patients will receive Ivonescimab combined with SBRT and modified FOLFIRINOX chemotherapy.
Maximum Tolerated Dose (MTD)
MTD is defined as the gradual increase in dose using 10 mg and 20 mg of ivonescimab to approach the maximum tolerated dose
Dose-Limiting Toxicity (DLT)
DLT is defined as unacceptable toxicities or adverse effects caused by a certain dose level of the drug, which prevent further dose escalation in participants.
Recommended Phase 2 Dose (RP2D)
The RP2D is the dose level of Ivonescimab recommended for use in Phase 2 clinical trials. This dose is typically chosen based on safety, tolerability, and preliminary efficacy data from Phase 1 trials.
Progression-Free Survival (PFS)
PFS defined as the time from the first dose of Ivonescimab to either the first radiographic evidence of disease progression or death from any cause, whichever occurs first.
Overall Survival (OS)
OS defined as the time from the first dose of Ivonescimab to the time of death from any cause.
Objective remission rate (ORR)
ORR defined as the proportion of subjects achieving a complete response (CR) or partial response (PR) among the total number of subjects, including an evaluation of both irradiated and non-irradiated lesions.
Disease control rate (DCR)
DCR defined as the proportion of subjects achieving CR, PR, or stable disease (SD) among the total number of subjects.
Duration of response (DOR)
DOR defined as the time from the first documented CR or PR to the first occurrence of progressive disease (PD) or death from any cause.
Click on the lead sponsor to view all of their trials.
