Advanced Solid Tumor
Conditions
Brief summary
A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.
Detailed description
This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic treatments.
Interventions
DRUGTCR-MAGE-A4 T-Cells
* Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses * MAGE-A4-directed T cell receptor-engineered T Cells
Sponsors
Shanghai Ming Ju Biotechnology Co., Ltd.
Peking University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 18-75 year-old, male or female 2. Voluntarily willing to participate in the study and sign the written informed consent form 3. Life expectation ≥12 weeks 4. European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion 5. Histologically-confirmed recurrent/metastatic advanced solid tumors 6. Radiologically-confirmed progression disease after at least one prior line of systematic treatment and no available standard of care at screening, judged by investigators 7. Fresh or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained MAGE-A4 positive 8. Human leukocyte antigen (HLA)-A\*02 allele matched 9. Per response evaluation criteria in solid tumors (RECIST) version 1.1, at least one measurable lesion 10. Adequate organ functions 11. Adequate venous access for APH 12. Non-hematological adverse events induced by previous treatment must have recovered to Grade ≤1 according to Common Terminology Criteria for Adverse Events (CTCAE), except for alopecia and peripheral neuropathy 13. Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1 year post infusion, and sperm donation is prohibited during the study 14. Women of childbearing potential must have negative serum human chorionic gonadotropin β (β-hCG) test result at screening and 48 hours prior to lymphodepletion
Exclusion criteria
1. Pregnant or lactating women 2. Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19) 3. Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH 4. Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors) 5. Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators 6. Systematic autoimmune disorders requiring long-term systematic treatment 7. Previously treated with any genetically engineered modified T cell therapy or other cell and gene therapy (CGT) 8. History of organ transplant 9. Uncontrolled or active infection within 72 hours prior to screening, APH, LD, or within 5 days prior to infusion 10. Subjects with other serious diseases that may restrict them from participating in this study 11. Clinically significant CNS disorders, such as epilepsy, stroke, Parkinson disease, etc 12. Grade ≥ 2 hemorrhage within 30 days prior to screening, or in need of longterm anticoagulants 13. Active digestive ulcer or gastrointestinal (GI) bleeding within 3 months prior to screening 14. Not satisfying wash-out period for APH 15. Previously allergic or intolerable to JWTCR001 or its components 16. Unable or unwilling to comply with the study protocol, judged by the investigators 17. Other situations implying that the subject might not be appropriate to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of dose-limiting toxicities (DLTs) | 28 days | Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWTCR001 infusion that met any of the following criteria. Any Grade ≥3 non-hematologic toxicity associated with JWTCR001 that has not resolved to Grade ≤2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators. Grade ≥3 hematological toxicities. Grade ≥3 anaphylaxis. Grade ≥3 infection did not resolve to Grade ≤2 within 7 days after anti-infective treatment. Grade ≥3 autoimmune toxicity during treatment. Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to Grade ≤2 within 72 hours. Grade ≥3 TCR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to Grade ≤2 within 72 hours. Grade 5 events of any nonmalignant cause. |
| Rate and severity of adverse events (AEs) and severe adverse events (SAEs) | 2 years | An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined. |
| Rate and severity of clinically-significant abnormalities in laboratory testings | 2 years | Clinically-significant abnormalities in laboratory testings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor efficacy-Duration of response (DOR) | 2 years | The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%). |
| Antitumor efficacy-Time to response (TTR) | 2 years | The time from the first infusion to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR. |
| Copy number of the vector transgene of JWTCR001 in peripheral blood | 2 years | The pharmacokinetic parameters of JWTCR001 will be evaluated by quantitative polymerase chain reaction (qPCR) for the copy number of the vector transgene of JWTCR001 in peripheral blood to evaluate T-cell expansion and persistence. |
| Antitumor efficacy-Objective response rate (ORR) | 2 years | The number of cases in which tumor size is reduced to complete response (CR) or partial response (PR) / the total number of evaluable cases (%). In the event of CR or PR, the subjects should confirm it no less than 4 weeks after the first evaluation. |
| Antitumor efficacy-Disease control rate (DCR) | 2 years | The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%). |
| Antitumor efficacy-Overall survival (OS) | 2 years | The period from the first infusion to any cause of death. |
| MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood | 2 years | The pharmacokinetic parameters of JWTCR001 will be evaluated by flow cytometry for the MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood to evaluate T cell expansion and persistence. |
| Antitumor efficacy-Progression-free survival (PFS) | 2 years | The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first. |
Countries
China
Contacts
Primary ContactLin Shen
Backup ContactChangsong Qi
Outcome results
None listed