Ivonescimab (PD-1/VEGF Bispecific Antibody) Plus Radiofrequency Ablation for Multiple Advanced Tumors After PD-1 Therapy Failure

NCT07095803 | Not Yet Recruiting Phase 2

• 1 other identifier: AK112-US-02
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if the combination of radiofrequency ablation (RFA) and Ivonescimab (PD-1/VEGF Bispecific Antibody) works to could reverse PD-1/PD-L1 resistance in patients with advanced tumors. It will also learn about the safety of this combination. The main questions it aims to answer are: Does the combination of RFA and Ivonescimab increase the objective response rate (ORR) of participants? What medical problems do participants have when taking the combination? Will the combination influence the progression-free survival time (PFS) and overall survival time and quality of life (QoL) of participants? Participants will: Patients received RGA treatment for less than three lesions. Patients were treated with Ivonescimab (20mg/kg Q3W, every 3 weeks) within 1 week before and after radiofrequency treatment until disease progression or intolerable toxicity occurred, or Ivonescimab was used for 2 years. Treatment effects will be evaluated every 9 weeks for 1 year and every 12 weeks thereafter.

Conditions

Multiple Advanced Tumors After PD-1 Therapy Failure

Keywords

Radiofrequency Ablation; Ivonescimab; Immunotherapy; Advanced Tumors

Outcome Measures

Primary Outcomes (1)

• The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria.

  Objective Response Rate (ORR)

  Efficacy was assessed every 9 weeks for 1 year and every 12 weeks thereafter (assessed up to 3 years).

Secondary Outcomes (4)

• Time from treatment start to progression by RECIST V.1.1.

  From date of treatment until the date of first documented progression, assessed up to 100 months.

• Time from treatment start to death of participants.

  From date of treatment until the date of death from any cause, whichever came first, assessed up to 100 months.

• Type, incidence, severity, onset and end time of adverse events (AE) evaluated according by the version 5.0 of NCI-CTCAE.

  Began at 30 days (±7 days) after the last study treatment to 1 year.

• Scores based on the assessment of FACT-P, version 4.

  Assessments were performed every 6 weeks during the screening period and during treatment (assessed up to 1 year).

Study Arms (3)

1

EXPERIMENTAL

Patients with advanced tumors who had been evaluated as effective on PD1 or PD1 combined with targeted therapy (CR,PR, or SD for more than 6 months on PD1 therapy) and then progressed on PD1 therapy or progressed less than 3 months after drug withdrawal;

Drug: Ivonescimab (20mg/kg Q3W); Procedure: radiofrequency ablation

2

EXPERIMENTAL

Patients with advanced tumors who had been evaluated as having a response to PD1 or PD1 combined targeted therapy (CR,PR, or SD for more than 6 months on PD1 therapy) and then progressed more than 3 months after drug withdrawal.

Drug: Ivonescimab (20mg/kg Q3W); Procedure: radiofrequency ablation

3

EXPERIMENTAL

Patients with advanced tumors who failed to respond to PD1 or PD1 combined with targeted therapy (the effect of PD1 therapy was PD or SD \< 6 months).

Drug: Ivonescimab (20mg/kg Q3W); Procedure: radiofrequency ablation

Interventions

Ivonescimab (20mg/kg Q3W) DRUG

Patients received intravenous everciximab (20mg/kg Q3W) within 1 week before and after radiofrequency ablation.

1; 2; 3

radiofrequency ablation PROCEDURE

Patients received radiofrequency treatment for less than three lesions.

1; 2; 3

Eligibility Criteria

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

You may qualify if:

• Voluntarily provide written informed consent
• Age ≥18 years old
• Histologically and/or cytologically confirmed advanced tumors as assessed by imaging or ultrasound
• ECOG score: 0-2
• At least one measurable lesion (according to RECIST criteria, the major diameter of non-lymph node lesions on CT scan ≥10 mm, and the minor diameter of lymph node lesions on CT scan ≥15 mm); There are other lesions that can be treated with radiofrequency
• Blood routine: Absolute Neutrophil Count (ANC) 1.5×10\^9/L, Platelet (PLT) ≥70×10\^9/L, Hemoglobin (HGB) ≥80g/L
• Liver function: serum Total Bilirubin (TBIL) ≤1.5× Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤3×ULN, and AST and ALT ≤5.0 ULN in patients with liver metastasis; Serum albumin ≥28 g/L
• Renal function: serum Creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/mi (using the standard Cockcroft-Gault formula) 9. Coagulation: International Normalized Ratio (INR) ≤1.5 /PT≤1.5×ULN, aPTT≤1.5×ULN
• Estimated survival time ≥3 months
• Use of a medically approved contraceptive method is required during the study treatment period and for at least 120 days after the end of the study, and sperm donation or cryopreservation for fertilization and reproduction is not permitted during this period
• Ability to adhere to study access schedules and other protocol requirements

You may not qualify if:

• Subjects with any severe and/or uncontrolled illness. These include:
• poor blood pressure control (systolic blood pressure ≥150 MMHG or diastolic blood pressure ≥100 MMHG); Poorly controlled diabetes (fasting blood glucose \[FBG\] \> 10mmol/L);
• with ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc≥470ms), and ≥ grade 2 congestive heart failure (New York Heart Association \[NYHA\] classification); And 3) severe active or uncontrolled infections (≥CTCAE grade 2 infection) requiring systemic antibacterial, antifungal, or antiviral therapy, including pulmonary tuberculosis infection.
• \) patients with a history of active tuberculosis; 5) If it is not controlled, ascites, pericardial effusion and pleural effusion still need repeated drainage
• A history of immunodeficiency, including HIV infection or other acquired or congenital immunodeficiency diseases
• Active autoimmune disease requiring systemic treatment within 2 years before the initiation of treatment, or autoimmune disease with potential recurrence or planned treatment as judged by the investigator; Exceptions include skin diseases that do not require systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema); Hypothyroidism due to autoimmune thyroiditis requires only stable doses of hormone replacement therapy. Well-controlled type I diabetes; Subjects who have had complete remission of childhood asthma without any intervention in adulthood; The investigator judged that the disease would not recur in the absence of an external trigger
• Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc., excluding IL-11 for thrombocytopenia) within 2 weeks before the first dose
• Subjects required systemic treatment with corticosteroids (\>10mg prednisone equivalent per day) or other immunosuppressive drugs within 14 days prior to study initiation. Subjects allowed topical, ocular, intra-articular, intranasal, and inhaled corticosteroids. Physiological alternative doses of systemic corticosteroids are allowed. Allowing short-term use of corticosteroids for prevention (e.g., contrast allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity from contact allergens)
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Known presence, leptomeningeal metastasis, spinal cord metastasis or compression
• History of abdominal fistula or gastrointestinal perforation related to anti-VEGF therapy; Esophagogastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, acute gastrointestinal bleeding, extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea within 6 months before the first administration of the drug
• Unhealed or poorly healed wounds or active ulcers
• Failure to resolve toxicity from previous antineoplastic therapy, defined as failure to return to NCI CTCAE version 5.0 grade 0 or 1
• Patients who underwent major surgical treatment, open biopsy, or significant traumatic injury within 28 days before the start of study treatment; Or have a wound or fracture that has not healed for a long time
• Severe hypersensitivity reaction after using monoclonal antibody; Those who were known to be allergic to the active ingredients or excipients of the study

Sponsors & Collaborators

• Sheng Zhang: lead

MeSH Terms

Interventions

Radiofrequency Ablation

Intervention Hierarchy (Ancestors)

Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Central Study Contacts

Dr. Sheng Zhang

CONTACT

86-18017317442; wozhangsheng@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: July 31, 2025
• Study Start: August 1, 2025
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share