Relapsed/Refractory Aggressive B-Cell Lymphoma
Conditions
Brief summary
This is a Phase I/II clinical study conducted in participants with relapsed/refractory aggressive B-cell lymphoma. The study aims to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SYS6055 Injection in participants with relapsed/refractory aggressive B-cell lymphoma, and to provide a basis for the recommended dosing regimen in subsequent studies.
Interventions
DRUGSYS6055
The dose will be selected based on the dose cohort, with a single administration.
Sponsors
Beijing Kangchuanglian Biopharmaceutical Technology Research Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, single-arm, dose-escalation study using a BOIN design. Four dose cohorts will be enrolled, and dose-limiting toxicities (DLTs) will be assessed after dosing in the first cycle (28 days). The Safety Monitoring Committee (SMC) will continuously review and monitor the safety of the investigational product.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Age ≥ 18 year, and voluntarily signed the Informed Consent Form (ICF); * 2\. Histologically confirmed aggressive B-cell lymphoma (defined according to the 5th edition of the WHO classification); * 3\. Patients with relapsed/refractory aggressive B-cell lymphoma who failed standard therapy, with CD19-positive tumor cells; * 4\. At least one measurable lesion according to the 2014 Lugano Response Criteria for Lymphoma; * 5\. ECOG performance status score of 0-1; * 6\. Expected survival of at least 3 months; * 7\. Adequate organ and bone marrow function; * 8\. Eligible participants (males and females) of reproductive potential must agree to use a reliable method of contraception (hormonal contraception, barrier method, or abstinence) with their partner during the trial and for at least 1 year after dosing. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. In addition, female participants must agree not to donate oocytes (eggs, ova) for assisted reproductive technology for 1 year after dosing, and male participants must agree not to donate sperm for assisted reproductive technology for 1 year after dosing; * 9\. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
* 1\. History of other malignancy within 3 years or concurrent other active malignancy (participants with cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc., may be enrolled); * 2\. Participants with bleeding diathesis, active bleeding, hemoptysis, or history of major bleeding within the previous 6 months; tumor invasion of major blood vessels shown by imaging (CT or MRI), or tumor judged by the investigator as highly likely to invade major blood vessels and cause fatal massive bleeding during the subsequent study period; * 3\. Participants with aggressive B-cell lymphoma involving the central nervous system; * 4\. Received autologous hematopoietic stem cell transplantation within 3 months prior to the first dose; * 5\. Previous allogeneic bone marrow transplantation, gene therapy, or adoptive cell therapy (including CAR-T therapy); * 6\. Received anti-PD-1, anti-PD-L1, or T-cell engager therapy within 3 months prior to the first dose; received fludarabine or bendamustine within 6 months prior to the first dose; * 7\. Adverse events from prior antineoplastic therapy have not recovered to CTCAE Version 6.0 grade ≤1 (except for alopecia or other toxicities without safety risk as judged by the investigator); * 8\. Received major surgery, chemotherapy, radical radiotherapy, antibody-based targeted therapy, imunotherapy, or other antineoplastic therapy within 28 days prior to dosing; or received palliative radiotherapy, chemotherapy, or small-molecule targeted therapy within 14 days prior to dosing; or received antineoplastic herbal preparations or traditional Chinese patent medicines within 14 days prior to dosing; * 9\. Simultaneously participating in another clinical trial, unless it is an observational (non-interventional) clinical trial or in the follow-up phase of an interventional trial (without impact on the follow-up data of this study); * 10\. Received live vaccine within 4 weeks prior to dosing; * 11\. Active bacterial, fungal, or viral infection prior to dosing. Individuals receiving prophylactic antimicrobial therapy without clinical manifestations of active infection prior to dosing may be considered for enrollment; * 12\. Autoimmune disease requiring systemic therapy; * 13\. History of central nervous system disease or current persistent central nervous system disease that may interfere with neurological assessments; * 14\. History of immunodeficiency or positive HIV antibody test during screening; * 15\. History of tuberculosis treatment within 2 years prior to dosing; history of active syphilis; * 16\. Active hepatitis B or hepatitis C during screening. Active hepatitis B is defined as HBsAg-positive and HBV DNA above the upper limit of normal (ULN). Active hepatitis C is defined as HCV antibody-positive and HCV RNA \> ULN; * 17\. History of severe cardiovascular disease; * 18\. Hypersensitivity or intolerance to the excipients of SYS6055 (mainly human albumin); * 19.Any other conditions in participants that may interfere with compliance with study procedures, are not in the best interest of participants, or may affect study results: e.g., history of psychiatric disorders, drug addiction or substance abuse, any other clinically significant diseases or conditions, etc.; * 20\. Pregnant or lactating female; * 21\. Any other reason judged by the investigator that the participant is not suitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicities (DLTs) | Dose-limiting toxicities (DLTs) will be assessed 28 days after the first dose. |
| Occurrence of Adverse Events (AE) and Serious Adverse Events (SAE) | Up to 24 months after administration of 6055 |
| Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) of SYS6055 | through study completion, an average of 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | through study completion, an average of 3 years | — |
| Time to Response（TTR ） | through study completion, an average of 3 years | — |
| Duration of Response (DoR) | through study completion, an average of 3 years | — |
| Progression-free survival (PFS) | through study completion, an average of 3 years | — |
| Overall Survival (OS) | hrough study completion, an average of 3 years | — |
| PK CD19-CAR copy number and CD19 CAR-T cell content of SYS6055 | 2 years | The levels of CD19 CAR RNA and DNA in peripheral blood will be determined by qPCR, with the proportion of CD19 CAR-T cells assessed by flow cytometry. |
| PK，CD19 CAR-T cell phenotypes | 2 years | CD19 CAR-T cell phenotypes will be analyzed by flow cytometry, including CD4/CD8 ratio, naïve cells, memory cells, and effector cells. |
| PD | 2 years | Levels of cytokines in peripheral blood (IL-6, IL-10, IFN-γ, TNF-α, etc.) |
| Immunogenicity, | 2 years | Incidence of anti-CD19-CAR antibodies and antiviral antibodies. |
| Viral shedding | 2 years | Peripheral blood, urine, saliva, and fecal samples will be collected at predefined time points for the assessment of viral shedding. |
| Replication-competent virus detection | 2 years | Peripheral blood, urine, saliva, and fecal samples will be collected at predefined time points for the assessment of viral shedding. |
| Viral integration site analysis | 2 years | Peripheral blood, urine, saliva, and fecal samples will be collected at predefined time points for the assessment of viral shedding |
Outcome results
None listed