Multiple Advanced Tumors After PD-1 Therapy FailurePhase 2NCT07095803
Ivonescimab (PD-1/VEGF Bispecific Antibody) Plus Radiofrequency Ablation for Multiple Advanced Tumors After PD-1 Therapy Failure
A Phase 2 study testing Ivonescimab (20mg/kg Q3W) and radiofrequency ablation in people with Multiple Advanced Tumors After PD-1 Therapy Failure, run by Sheng Zhang.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Advanced Tumors After PD-1 Therapy Failure
- What is being tested?
- Ivonescimab (20mg/kg Q3W) and radiofrequency ablation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2025to 1 Feb 2027
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
- 4) patients with a history of active tuberculosis; 5) If it is not controlled, ascites, pericardial effusion and pleural effusion still need repeated drainage
- Active hepatitis (transaminase did not meet the inclusion criteria, hepatitis B reference: HBV DNA≥2000 IU/ml or ≥104 copies /ml; Hepatitis C reference: HCV RNA≥2000 IU/ml or ≥104 copies /ml; After nucleotide antiviral therapy, those below the above criteria can be enrolled). Chronic hepatitis B virus carriers with HBV DNA < 104 IU/ml could only be enrolled if they received antiviral therapy at the same time during the trial
- A history of immunodeficiency, including HIV infection or other acquired or congenital immunodeficiency diseases
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- 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
- Are participating or have participated in other clinical investigators within 4 weeks before study initiation
- Have received a live vaccine within 30 days before the first dose, or plan to receive a live vaccine during the study
- Patients with a history of severe allergy
- At risk of bleeding, or coagulopathy, or receiving thrombolytic therapy
- Persons with a history of psychotropic drug abuse and inability to quit or mental disorders
- Subjects who, in the investigator's judgment, had a concomitant medical condition that seriously jeopardized the safety of the subjects or interfered with the completion of the study, or who were deemed to be ineligible for enrollment for any other reason. A clear history of a previous neurological and mental disorder, such as dementia, epilepsy, or seizure prone
- The presence of concomitant diseases (such as severe diabetes mellitus, thyroid disease, and psychosis), or serious and/or unstable medical, psychiatric, or other conditions (including laboratory abnormalities) that, in the judgment of the investigators, seriously compromise the safety of the subjects or prevent the subjects from completing the study, or the presence of serious and/or unstable medical, psychiatric, or other conditions (including laboratory abnormalities) that affect the safety of the patients or affect the informed consent of the patients; Or the presence of any psychological, family, sociological or geographical factors that affect the study protocol and follow-up plan
- The investigator decided that he was not suitable to participate in the trial for any reason
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Ivonescimab (PD-1/VEGF Bispecific Antibody) Plus Radiofrequency Ablation for Multiple Advanced Tumors After PD-1 Therapy Failure: A Multicohort, Multicenter, Single-Arm Phase II Study
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?
Read more
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.
- Being tested
- Ivonescimab (20mg/kg Q3W), radiofrequency ablation
- Keywords
- Radiofrequency Ablation, Ivonescimab, Immunotherapy, Advanced Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab (20mg/kg Q3W)Drug
Patients received intravenous everciximab (20mg/kg Q3W) within 1 week before and after radiofrequency ablation.
radiofrequency ablationProcedure or surgery
Patients received radiofrequency treatment for less than three lesions.
| Study group | Role | What they receive |
|---|---|---|
| 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; Receives: 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. Receives: 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). Receives: Drug: Ivonescimab (20mg/kg Q3W); Procedure: radiofrequency ablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria.
Objective Response Rate (ORR)
Measured: 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.
Progression-free survival(PFS)
Measured: From date of treatment until the date of first documented progression, assessed up to 100 months.
Time from treatment start to death of participants.
Overall Survival(OS)
Measured: 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.
Evaluation of safety
Measured: Began at 30 days (±7 days) after the last study treatment to 1 year.
Scores based on the assessment of FACT-P, version 4.
Quality of Life (QoL) among participants. Scores based on the assessment of FACT-P, version 4, range from 0-156 points. Higher scores mean a better outcome.
Measured: Assessments were performed every 6 weeks during the screening period and during treatment (assessed up to 1 year).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start1 Aug 2025 (estimated)
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Advanced Tumors After PD-1 Therapy FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheng Zhang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sheng Zhang, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07095803
- Sponsor's protocol ID
- AK112-US-02
- Status last verified
- Jul 2025
- First submitted
- 15 Jul 2025
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ivonescimab (PD-1/VEGF Bispecific Antibody) Plus Radiofrequency Ablation for Multiple Advanced Tumors After PD-1 Therapy Failure: A Multicohort, Multicenter, Single-Arm Phase II Study
- ClinicalTrials.gov ID
- NCT07095803
- Acronym / sponsor ID
- AK112-US-02
- Keywords
- Radiofrequency Ablation, Ivonescimab, Immunotherapy, Advanced Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Sheng ZhangUniversity, hospital or other
- Study start
- 1 Aug 2025 (estimated)
- Primary completion
- 1 Feb 2026 (estimated)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 31 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Ivonescimab (20mg/kg Q3W), Procedure: radiofrequency ablationPatients 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; |
| 2 | Experimental | Drug: Ivonescimab (20mg/kg Q3W), Procedure: radiofrequency ablationPatients 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. |
| 3 | Experimental | Drug: Ivonescimab (20mg/kg Q3W), Procedure: radiofrequency ablationPatients 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (24 listed)
- Subjects with any severe and/or uncontrolled illness. These include:
- 4) patients with a history of active tuberculosis; 5) If it is not controlled, ascites, pericardial effusion and pleural effusion still need repeated drainage
- Active hepatitis (transaminase did not meet the inclusion criteria, hepatitis B reference: HBV DNA≥2000 IU/ml or ≥104 copies /ml; Hepatitis C reference: HCV RNA≥2000 IU/ml or ≥104 copies /ml; After nucleotide antiviral therapy, those below the above criteria can be enrolled). Chronic hepatitis B virus carriers with HBV DNA < 104 IU/ml could only be enrolled if they received antiviral therapy at the same time during the trial
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivonescimab (20mg/kg Q3W)Patients received intravenous everciximab (20mg/kg Q3W) within 1 week before and after radiofrequency ablation. | Drug | 1, 2, 3 |
| radiofrequency ablationPatients received radiofrequency treatment for less than three lesions. | Procedure or surgery | 1, 2, 3 |
Primary outcome
The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria.
Time frame: Efficacy was assessed every 9 weeks for 1 year and every 12 weeks thereafter (assessed up to 3 years).
Objective Response Rate (ORR)
4 secondary outcomes
Time from treatment start to progression by RECIST V.1.1.
Time frame: From date of treatment until the date of first documented progression, assessed up to 100 months.
Time from treatment start to death of participants.
Time frame: 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.
Time frame: Began at 30 days (±7 days) after the last study treatment to 1 year.
Scores based on the assessment of FACT-P, version 4.
Time frame: Assessments were performed every 6 weeks during the screening period and during treatment (assessed up to 1 year).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivonescimab (20mg/kg Q3W) and radiofrequency ablation in people with Multiple Advanced Tumors After PD-1 Therapy Failure, run by Sheng Zhang.
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 11 inclusion and 24 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: opening soon, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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 Dr. Sheng Zhang (86-18017317442, wozhangsheng@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients who achieved CR or PR according to RECIST V.1.1 criteria. (time frame: Efficacy was assessed every 9 weeks for 1 year and every 12 weeks thereafter (assessed up to 3 years).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2025.