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Pancreatic CancerPhase 1/2NCT06844422

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

A Phase 1/2 study testing Ivonescimab in people with Pancreatic Cancer, run by Shandong Cancer Hospital and Institute at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pancreatic Cancer
What is being tested?
Ivonescimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteChina
Study dates
8 Feb 2025to 18 Feb 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jinbo Yue, Doctor contact

0531-67626442

jbyue@sdfmu.edu.cn

China1 site, 1 recruiting

  • Shandong Cancer Hospital and Institute

    Jinan, Shandong, 0531

    Jinbo Yue, Doctor, 0531-67626442, jbyue@sdfmu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Adapted Guided Stereotactic Body Radiotherapy Combined With Chemotherapy and Enhancement of Novel Drug Ivonescimab for Pancreatic Cancer (ASCEND) -A Single-Arm Phase Ib/II Trial

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.

Read the detailed description

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.

Being tested
Ivonescimab
Keywords
Adapted Guided Stereotactic Body Radiotherapy, Chemotherapy, Ivonescimab, Pancreatic Cancer
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvonescimabDrug

    Also called Adapted Guided Stereotactic Body Radiotherapy, Chemotherapy

    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 groups in NCT06844422
Study groupRoleWhat they receive
Stereotactic Body Radiotherapy Combined with Chemotherapy and Enhancement of Novel Drug IvonescimabExperimental1. 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.
Receives: Drug: Ivonescimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 1 years

  2. 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.

    Measured: 1 years

  3. 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.

    Measured: 1 years

  4. 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.

    Measured: 3 years

Secondary outcomes (6)

  1. Overall Survival (OS)

    OS defined as the time from the first dose of Ivonescimab to the time of death from any cause.

    Measured: 3 years

  2. 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.

    Measured: 3 years

  3. Disease control rate (DCR)

    DCR defined as the proportion of subjects achieving CR, PR, or stable disease (SD) among the total number of subjects.

    Measured: 3 years

  4. 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.

    Measured: 3 years

  5. Local Control Rate (LCR)

    LCR defined as the proportion of patients whose tumors have not progressed locally after receiving treatment.

    Measured: 3 years

  6. Adverse Events (AEs)

    AEs assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2025
  2. Study start8 Feb 2025
  3. Primary completion18 Feb 2028 (estimated)
  4. Study completion18 Feb 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06844422
Sponsor's protocol ID
SDZLEC2024-414-02
Status last verified
Apr 2026
First submitted
19 Feb 2025
Last updated
28 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39661367

  • 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.

    PubMed 39661345

  • 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.

    PubMed 37879536

  • 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.

    PubMed 38642937

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

    PubMed 39073550

  • 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.

    PubMed 38820549

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ivonescimab in people with Pancreatic Cancer, run by Shandong Cancer Hospital and Institute at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jinbo Yue, Doctor (0531-67626442, jbyue@sdfmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 1 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06844422, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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