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.
This study is a single-arm, Phase Ib/II clinical trial designed to evaluate the safety and efficacy of Ivonescimab, a bispecific antibody targeting both programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF), in combination with stereotactic body radiotherapy (SBRT) and chemotherapy for locally advanced pancreatic cancer (LAPC). The trial will recruit 37 patients with LAPC, with Phase Ib focusing on determining the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended Phase II dose (RP2D) of Ivonescimab. In the Phase Ib portion, a dose-escalation design using the 3 + 3 methodology will be employed over a 4-week period to establish the RP2D for Ivonescimab. The goal is to identify the optimal dose that can be safely administered to patients without excessive toxicity. Once the RP2D is determined, the trial will proceed to Phase II. Phase II will evaluate the efficacy of Ivonescimab at the RP2D in combination with SBRT and chemotherapy, with the primary endpoint being the median progression-free survival (mPFS) of patients with LAPC. Initially, participants will receive Ivonescimab combined with SBRT (25-50 Gy in 5 fractions) over two weeks. Following this, they will undergo up to 8-10 cycles of Ivonescimab in combination with modified FOLFIRINOX chemotherapy, which includes oxaliplatin, irinotecan, leucovorin, and fluorouracil. Patients will continue maintenance treatment with Ivonescimab based on individual tolerance for up to 12 months, or until intolerable toxicity or disease progression occurs. The study aims to assess both the safety and therapeutic efficacy of this novel combination treatment as a first-line approach for LAPC. Results from this Phase Ib/II study will provide critical data for the development of future treatment strategies for LAPC, potentially improving patient outcomes by targeting both the immune response and tumor vasculature.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
1. 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.
Shandong Cancer Hospital and Institute
Jinan, Shandong, China
RECRUITINGMaximum 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
Time frame: 1 years
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.
Time frame: 1 years
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.
Time frame: 1 years
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.
Time frame: 3 years
Overall Survival (OS)
OS defined as the time from the first dose of Ivonescimab to the time of death from any cause.
Time frame: 3 years
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.
Time frame: 3 years
Disease control rate (DCR)
DCR defined as the proportion of subjects achieving CR, PR, or stable disease (SD) among the total number of subjects.
Time frame: 3 years
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.
Time frame: 3 years
Local Control Rate (LCR)
LCR defined as the proportion of patients whose tumors have not progressed locally after receiving treatment.
Time frame: 3 years
Adverse Events (AEs)
AEs assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Time frame: 3 years
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