Phase I study of non-viral gene-modified CAR-T cell therapy for ewing sarcoma or malignant solid tumors with expression of EPHB4 receptor

JRCT ID: jRCT2033230299

Registered date:18/08/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Ewing's sarcoma or solid tumors diagnosed as advanced relapsed with no standard treatment or refract
• Date of first enrollment: 01/10/2023
• Target sample size: 18
• Study type: Interventional
• Intervention(s): Administration of CAR-T cells produced from eripheral blood. After pretreatment, the target dose assigned to the subject as CAR-expressing T cells(range:2.7x10^5 cells/kg or 2.7x10^4 cells/kg or 2.7x10^6 cells/kg) is intravenously infused.

Outcome(s)

• Primary Outcome: Incidence of DLTs from the start of pretreatment to 28 days after AP8901 administration

Secondary Outcome

Incidence of adverse events
ORR:Objective response rate
PFS:Progression-free survival
DoR :Duration of response
DCR:Disease control rate
OS:Overall survival
Pharmacokinetics

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Patients who have voluntarily provided written consent for participation in the study
2.Patients aged 18 years or older at the time of providing informed consent
3.Patients diagnosed with ewing sarcoma or solid tumor who confirmed metastatic or recurrent
4.Patients with recurrent or metastatic canser that is refractry or intolerant to standard therapy
5.Patients who have measurable disease or evaluable disease according to RECIST version 1.1
6.Tumor must be EPHB4 receptor 1% or more positive by immunohistochemistry
7.Patients with PS(ECOG) of 0 to 1
8.Life expectancy of at least 3 months
9.Patients who have adequate organ function and whose latest laboratory results within 7 days prior to enrollment meet all the following criteria
(1)ANC >= 1000 /mm3
(2)Platelet count >= 100,000/ mm3
(3)Hemoglobin >= 8.0 g/dL
(4)Serum creatinine <= 2.0 mg/dL or calculated (with the Cockcroft-Gault formula) or measured creatinine clearance >= 50 mL/min
(5)Total bilirubin <= 2.0 mg/dL
(6)AST, ALT<=100 IU/L
(7)Prothrombin time<=1.5xULN
(8)Activated partial thromboplastin time<=1.5xULN
10.Non-pregnant patient.In female of childbearing potential, negative for pregnancy test within 7 days prior to enrollment
11.In female of childbearing potential or male partner, patients who agree to contraception for the period from informed consent to at least 12 months after administration of AP8901
12.Patients willing to participate in a long-term observational study

Exclude criteria

1.Patients with other malignancies or history within 2 years prior to enrollment
Note: Patients with carcinoma in situ are allowed.For example basal cell carcinoma,squamous cell carcinoma,carcinoma in situ of the cervix,non-invasive breast cancer,completely resected intramucosal gastric carcinoma
Note: Patients with bilateral breast cancer are allowed if one of the two has completed radical treatment and has been disease-free for at least 5 years
2.Patients with brain metastases or spinal cord compression
Note: Patients who are asymptomatic and do not require treatment are allowed
3.Lactating patients
4.Patients who are receiving systemic steroids or immunosuppressive drug therapy
Note: A dose <= 10 mg / day of prednisolone is allowed
5.Patients who require any prior anticancer drug (including chemotherapy, molecular targeted therapy, antibody therapy, hormone therapy,endocrine therapy or immunotherapy), other unapproved drugs, surgical treatment, radiotherapy or radiopharmaceutical within 14 days prior to enrollment
6.Patients who received a live virus vaccine within 28 days prior to enrollment.
7.Patients with HIV infection
8.Patients with HTLV infection
9.Patients who have the following infectious diseases
-HBsAg-positive
-HBsAb-positive or HBcAb-positive
Note: Patients with HBV-DNA level < 20 IU/mL (1.3 logIU/mL) are allowed.
10.Patients with active HCV infection
11.Patients with active bacterial or viral infections or suspected of having these infections
12.Patients with at least one prior treatment for any gene therapy
Note: Patients with mRNA and DNA vaccines are allowed
13.Patients with a history of allogeneic HSCT
14.Patients with active autoimmune disease
15.Patients who have pericardial, ascites, or pleural effusions requiring treatment
16.Patients with a history or complication of cerebrovascular disease (stroke or hemorrhage) or transient ischemic attack within 180 days prior to enrollment
17.Patients with a history or complications of thrombosis or thromboembolism (pulmonary artery embolism or deep vein thrombosis)
Note: Patients who have been diagnosed for at least 90 days and have no relapse concerns are allowed
18.Patients with serious cardiovascular disease (prior or concurrent congestive heart failure, unstable angina, or myocardial infarction of degree III or higher by NYHA criteria or severe arrhythmia within 6 months prior to enrollment)
19.Patients with interstitial lung disease/pulmonary inflammation or a history of (non-infectious) interstitial pneumonia/pulmonary inflammation requiring steroid administration
20.Patients with a history of serious immune-related adverse events (irAE) due to immune checkpoint inhibitors
Note: Patients with a history of endocrine dysfunction that can be controlled with hormone replacement therapy (but not more than 10 mg/day of prednisolone) are allowed
21.Patients with a history of hypersensitivity reactions to ingredients or additives used in the investigational product (Cryo Stor CS10 ,human serum albumin )
22.Patients with a history of hypersensitivity reactions to pretreatment
23.Patients unable to comply with the schedule
24.Patients who are deemed inappropriate by the investigator or sub-investigator

Related Information

• Primary Sponsor: Naito Yoichi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development