Ivonescimab: 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.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria:
1. Pathologically or cytologically confirmed unresectable LAPC, as defined by the 8th edition of the American Joint Committee on Cancer (AJCC);
2. Age between 18 and 80 years;
3. At least one measurable pancreatic cancer lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
5. Life expectancy of at least 3 months;
6. Adequate hematological, renal, and hepatic function, as defined by the following criteria (within 14 days prior to enrollment): (1) Hemoglobin (Hb) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.0 × 10\^9/L; Platelet count (PLT) ≥ 75 × 10\^9/L; (2) No significant organ dysfunction, with the following criteria: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or direct bilirubin ≤ ULN if total bilirubin \> 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alkaline phosphatase (ALP) ≤ 2.5 × ULN, or ≤ 2.5 × ULN for the liver fraction if ALP \> 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance (using the MDRD formula) ≥ 40 mL/min if serum creatinine is \> 1.5 × ULN; Urine protein \< 2+, or if ≥ 2+ on dipstick, 24-hour urine protein must be \< 2 g or the urine protein-to-creatinine ratio (UPC) must be \< 2; International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;
7. Ability to provide tissue and blood samples for translational research;
8. Ability to comprehend study details and provide written informed consent.
Exclusion Criteria:
1. History of any malignant tumors within the past 5 years, except for cured localized tumors;
2. 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;
3. Previous treatment with drugs targeting other stimulatory or co-inhibitory T-cell receptors;
4. Prior radiotherapy within 2 weeks before enrollment;
5. Known allergy to Ivonescimab or its excipients;
6. Pregnancy or lactation;
7. Current or planned use of strong CYP3A4/5 or CYP1A2 inducers or strong CYP3A4/5 inhibitors;
8. Requirement for oral vitamin K antagonists for anticoagulation. Low-dose warfarin (≤ 2 mg/day) and other low-dose anticoagulants for maintaining central venous access or preventing deep vein thrombosis are permitted. Low-molecular-weight heparin is also permitted;
9. Conditions affecting oral medication administration, such as a history of gastrointestinal perforation or fistula within the past 6 months, history of intestinal obstruction, extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea.
Primary outcome measure(s)
Maximum Tolerated Dose (MTD) — 1 years 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) — 1 years 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) — 1 years 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) — 3 years 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.
Trial sites (1)
Facility
City
Region
Status
Shandong Cancer Hospital and Institute
Jinan
Shandong
Recruiting
More Shandong Cancer Hospital and Institute trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.