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

NCT06844422 | Recruiting Phase 1

• 1 other identifier: SDZLEC2024-414-02
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pancreatic Cancer

Keywords

Adapted Guided Stereotactic Body Radiotherapy; Chemotherapy; Ivonescimab; Pancreatic Cancer

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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.

  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.

  3 years

Secondary Outcomes (6)

• Overall Survival (OS)

  3 years

• Objective remission rate (ORR)

  3 years

• Disease control rate (DCR)

  3 years

• Duration of response (DOR)

  3 years

• Local Control Rate (LCR)

  3 years

Study Arms (1)

Stereotactic Body Radiotherapy Combined with Chemotherapy and Enhancement of Novel Drug Ivonescimab

EXPERIMENTAL

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.

Drug: Ivonescimab

Interventions

Ivonescimab DRUG

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.

Also known as: Adapted Guided Stereotactic Body Radiotherapy, Chemotherapy

Stereotactic Body Radiotherapy Combined with Chemotherapy and Enhancement of Novel Drug Ivonescimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Life expectancy of at least 3 months;
• 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;
• Ability to provide tissue and blood samples for translational research;
• Ability to comprehend study details and provide written informed consent.

You may not qualify if:

• 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;
• Known allergy to Ivonescimab or its excipients;
• Pregnancy or lactation;
• Current or planned use of strong CYP3A4/5 or CYP1A2 inducers or strong CYP3A4/5 inhibitors;
• 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;
• 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.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, 0531, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 39661367 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.

  PMID: 39661345 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.

  PMID: 37879536 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.

  PMID: 38642937 BACKGROUND

• Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29.

  PMID: 39073550 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.

  PMID: 38820549 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Jinbo Yue, Doctor

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinbo Yue, Doctor

CONTACT

0531-67626442; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department Radiation Oncology

Model Details: 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.

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 25, 2025
• Study Start: February 8, 2025
• Primary Completion (Estimated): February 18, 2028
• Study Completion (Estimated): February 18, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)