Using Ivocizumab to treat various advanced rare tumors

Ivonescimab (PD-1/VEGF Bispecpecial Antibody) in the Treatment of Multiple Advanced Tumors: a Multi-cohort, Multi-center, Single-arm Phase II Study

This study is testing if a new treatment called Ivocizumab can help people with different types of advanced rare tumors feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: Ivonescimab, ebraxizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06683846 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of Ivocizumab in treating multiple advanced rare tumors across various cohorts. It is a prospective, multi-cohort phase II study that focuses on assessing the objective response rate (ORR) as the primary endpoint, while also measuring secondary outcomes such as imaging progression-free survival (PFS), overall survival (OS), quality of life (QoL), and safety. The trial includes a diverse range of tumor types, including Paget's disease, paraganglioma, pheochromocytoma, and several others, with participants receiving treatment and undergoing regular evaluations. The study is designed to provide insights into the potential benefits of immunotherapy for these rare conditions.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals with histologically confirmed advanced rare tumors, specifically those classified under the study's defined cohorts.

Not a fit: Patients with early-stage tumors or those not meeting the specific tumor type criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced rare tumors that currently have limited treatment options.

How similar studies have performed: While the use of immunotherapy for rare tumors is an emerging field, there have been some promising results in similar studies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Individuals able to understand and give written informed consent.
* Histologically or cytologically confirmed cancer of one of the following types:

PAGET's disease of scrotum with infiltrating sweat gland carcinoma Paraganglioma Pheochromocytom, Renal angiomyolipoma Malignant perivascular epithelioid cell tumor, Rhabdomyosarcom Other sarcoma rather than rhabdomyosarcom

* Stage IV disease
* Adequate performance status (ECOG 0-2)
* Expected survival ≥ 3 months.
* Measurable disease by CT or MRI, Or lesions with skin infiltration.
* Adequate hematology without ongoing transfusional support (hemoglobin \> 9 g/dL, absolute neutrophil count (ANC) \> 1,500 per mm\^3, platelets \> 100,000 per mm\^3).
* Adequate renal and hepatic function (creatinine ≤ 2.0 x institutional upper limit of normal (IULN), bilirubin ≤ 1.5 IULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
* Adequate coagulation function: International Normalized Ratio (INR) ≤1.5 /PT≤1.5×ULN, aPTT≤1.5×ULN.
* Willing to use a medically approved contraceptive method from the enrollment to at least 120 days after the end of the study, and sperm donation to another person or cryopreservation for fertilization and reproduction is not permitted during this period.
* Ability to comply with research visit schedules and other protocol requirements.

Exclusion Criteria:

* With any severe and/or uncontrolled disease. Including: (1)Poor blood pressure control (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg); (2) poor control of diabetes (fasting blood sugar \[FBG\] \>10mmol/L);

  ≥2 grade myocardial ischemia or myocardial infarction, arrhythmia (QTc≥470ms), and ≥2 grade congestive heart failure (NYHA classification); (3)active or uncontrolled severe infections requiring systemic antibacterial, antifungal, or antiviral treatment (≥CTCAE 2-level infection), including tuberculosis infection; A history of active tuberculosis; (4)Uncontrolled ascites, pleural effusion, or pericardial effusion that require repeated drainage;
* With active hepatitis (transaminase levels not meeting inclusion criteria; HBV reference: HBV DNA≥2000 IU/ml or ≥10\^4 copies/ml; HCV reference: HCV RNA≥2000 IU/ml or ≥10\^4 copies/ml; after nucleoside analog antiviral therapy below the above standard, can be included; chronic hepatitis B virus carrier, HBV DNA\<10\^4 IU/ml, must be treated with antiviral drugs during the trial period to be eligible for enrollment);
* History of immunodeficiency, including HIV positive or subjects with other acquired or congenital immunodeficiency diseases;
* Active autoimmune disease requiring systemic treatment within the past two years, or subjects with an autoimmune disease that the investigator judges may recur or is planned for treatment; except: non-systemic treatment of skin diseases (e.g. vitiligo, alopecia, psoriasis or eczema); autoimmune thyroiditis-induced hypothyroidism requiring stable dose replacement therapy with hormones; 13. Subjects who have experienced severe hypersensitivity reactions after using monoclonal antibodies; individuals who are known to be allergic to the active ingredients or excipients of the study drug;
* Have participated or are currently participating in another clinical study within the past 4 weeks prior to study entry;
* Received a live vaccine within the past 30 days prior to the first dose or plan to receive a live vaccine during the study;
* History of severe allergies;
* At risk of bleeding, or with impaired coagulation function, or currently receiving thrombolytic therapy;
* History of substance abuse with an inability to abstain or a history of mental illness;
* Subjects who, in the opinion of the investigator, have a serious underlying condition that would endanger the subject's safety or impair the subject's ability to complete the study, or who, in the opinion of the investigator, have other reasons not to be enrolled; Subjects who have a history of a clearly defined neurological or psychiatric disorder, such as dementia, epilepsy, or a history of seizure susceptibility;
* Subjects who, in the opinion of the investigator, have a serious underlying condition that would endanger the subject's safety or impair the subject's ability to complete the study (such as severe diabetes, thyroid disorders, and mental illness), or who have a serious and/or unstable medical, psychological, or other condition (including laboratory abnormalities) that would affect the subject's safety or the subject's ability to provide informed consent, or who have any condition that would affect the study protocol and follow-up plan, including psychological, familial, social, or geographic factors;

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Cancer Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Hongxia Wang, Doctor — Fudan University
• Study coordinator: Sheng Zhang, Doctor

Conditions Pheochromocytoma/Paraganglioma; Rhabdomyosarcoma; Paget Disease, Extramammary; Renal Angiomyolipoma; Perivascular Epithelioid Cell Tumor, Malignant; Sarcoma; Urachal Cancer; Neuroendocrine Cancer