A Phase I/Ⅱ a Clinical Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Efficacy of Sc610 Cell Injection in the Treatment of Advanced Urinary System Tumors
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malignant Tumor of Urinary System (Disorder)
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 45
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an phase I/IIa, open-lable, single-arm, single-dose escalation and multiple-dose extention clinical study of cell therapy designed to observe and evaluate the tolerance, the pharmacokinetic characteristics, the safety and the efficacy of Sc610 cell injection in the treatment of advanced tumor of urinary system.
Detailed Description
This study consists of two phases: the first phase will be the dose exploration phase (Phase I), followed by the dose extension phase (Phase II). In phase I, 3 subjects are enrolled for 1st treatment group, starting with single dose of Sc610 cell injection of 5.0x10\^8. If there is no dose limiting toxicity (DLT) observed, 3 subjects are enrolled into treatment groups successively in sequential order of: 1) group 2: Single dose of Sc610 1.5x10\^9; 2) group 3: Single dose of Sc610 5x10\^9; and 3) gorup 4: Single dose of Sc610 1.5x10\^10. Starting from the completion of Sc610 reinfusion for first subject of the 1st dose group, the subject will be observed for no less than one week. If no serious toxic and adverse events occurrs, Sc610 reinfusion for the second and third subjects will be performed. If no DLT occurrs by the 14th days after completion of reinfusion for the 3rd subject, The study will proceed to the next treatment group. If DLT is observed in 1/3 of enrolled subjects, another 3 subjects will be enrolled. In any of the dose groups, if ≤1/6 subjects have DLT, subject enrollment for the next treatment group will start. If DLT occurs in ≥2/6 of subjects, the number of subjects in the previous dose group shall be reviewed. If there were only 3 subjects, 3 more subjects will be enrolled. If DLT occurs in ≤1/6 subjects, the dose will be defined as the maximum tolerable dose (MTD), and the dose escalation phase of the study will be completed. If DLT occurs in ≥2/6 subjects in the first dose group, a dose reduction exploration will be performed or the study will be terminated upon decision made by the Safety Committee. In phase II, If no dose limiting toxicity event occurred upon the completion of treatment in each of the 4 groups. Researcher will decide to select 2-4 dose groups for dose extension study and will enroll 5-8 subjects for each group. Certain subjects have the option to receive multiple rounds of Sc610 treatment: 1) Subjects with unconfirmed disease progression (non iCPD, i.e. iUPD, iSD, iPR) as assessed by the response to the cell treatment by medical imaging of last round of treatment can enter multiple rounds of treatment. Subjects with complete remission (iCR) will be allowed to receive one consolidation treatment；Subjects whose response to the cell treatment as assessed by medical imaging are disease progression (iCPD), and the investigator judge that the subjects would be unable to benefit from the treatment of this study, and need to receive a new treatment or change the treatment method, will fall off/withdraw from the trial. 2) Before entering the next round of treatment each time, the percentage of PD-1+T cells in total T cells need to be assayed first, and peripheral blood monocytes apheresis can be performed if the detection result is≥18% (PBMCs≥3 x10\^9). The procedures of preparation, reinfusion, and follow-ups after reinfusion of Sc610 cell injection are the identical as before. 3) If toxic reaction related to Sc610 greater than grade 3 cells is observed in previous dose (round) of treatment, the dose of next round will be reduced; If adverse events above grade 3 still occur after dose reduction, the investigator will make a comprehensive judgment on whether to terminate the study of this subject. 4) Multiple round treatment is a treatment cycle every 12 weeks. After treatment, follow up until the disease progresses, or start a new anti-tumor treatment, or fall off, or withdraw from the trial.
Investigators
Hai Huang
Director of Department of Urology Surgery
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years old, regardless of gender;
- •Expected survival \>3 months;
- •The physical condition score of the Eastern American Oncology Collaboration Group (ECOG) equal to 0 or 1;
- •Patients with pathologically confirmed, locally advanced, or recurrent metastatic advanced urinary system malignant tumors, failed in standard treatment, disease development after multi-line treatments, and cannot be surgically removed, including:
- •Renal cell carcinoma: clear cell carcinoma, papillary renal cell carcinoma, chromophobe cell carcinoma, etc;
- •Urothelial carcinoma: including renal pelvis, ureter, bladder, or urethra orginated;
- •Prostate adenocarcinoma.
- •According to iRECIST standard, there exists at least one measurable tumor lesion as shown by CT or MRI. Measurable tumor lesions are defined as the longest diameter ≥10mm and scanning thickness ≤ 5.0mm. For lymph node lesions, the short diameter ≥ 15mm;
- •The proportion of peripheral blood PD-1+T cells in total T cells ≥ 18%; and voluntarily accept the apheresis of peripheral blood mononuclear cells for the preparation of Sc610 cell injection;
- •Sufficient bone marrow and organ functions:
Exclusion Criteria
- •Intracranial metastasis or meningeal metastasis with clinical symptoms, or other evidence indicating that the intracranial metastasis or meningeal metastasis of the patient has not been controlled, and the vertebral body metastasis that is known or suspected to cause spinal cord compression, with which the investigator judge that the patient is not suitable for study enrollment;
- •Patients who have had or are currently suffering from other malignant tumors within 2 years before signing the contract, excluding cured patients with basal cell skin cancer, in situ cervical carcinoma, and in situ lung cancer;
- •Patients treated with PD-L1 monoclonal antibody (including but not limited to atezolizumab and duvalizumab) within 12 weeks before collection;
- •Those who have active infection within one week before single collection and need systematic anti infection treatment at present ;
- •People with interstitial lung disease ;
- •Patients who have received immunotherapy and have ≥ grade 3 IRAE;
- •Patients with active or ever suffered from autoimmune diseases with the possibility of recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except patients with clinically stable autoimmune thyroid diseases and well controlled type I diabetes ;
- •The adverse reaction of previous anti-tumor treatment has not recovered to CTCAE 5.0 grade evaluation ≤ 1 (except for the toxicity that the researcher judges is without risk for safety);
- •Have received anti-tumor treatment within 2 weeks before apheresis, including but not limit to systemic chemotherapy, radiotherapy, immunotherapy, etc; Nitrosourea or mitomycin C is defined within 6 weeks before apheresis;
- •Have received systemic glucocorticoid (prednisone ≥ 10mg/day or equivalent dose of the same type of drug) or other immunosuppressants within 2 weeks before apheresis; The following conditions are exempted: intermittent use of glucocorticoids in local, eye, joint cavity, nose, and inhalation; and short term use of glucocorticoid for preventive treatment (such as prevention of contrast agent allergy);
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 12 weeks after single dose of cell reinfusion
Including cases of complete response (CR) and of partial response (PR).
Secondary Outcomes
- Progression-Free Survival (PFS)(12 weeks after single dose of cell reinfusion)
- Duration of Response (DOR)(12 weeks after single dose of cell reinfusion)
- Overall survival (OS)(From single dose of cell reinfusion to death)
- Adverse events (AEs)(24 weeks after single dose of cell reinfusion)
- Disease Control Rate (DCR)(12 weeks after the single dose of cell reinfusion)
- Detection of Lentivirus Copy Number(12 weeks after single dose of cell reinfusion)