Clinical Study of SYS6055 Injection in Participants With Relapsed/Refractory Aggressive B-Cell Lymphoma

Official title

A Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of SYS6055 Injection in Participants With Relapsed/Refractory Aggressive B-Cell Lymphoma

Overview

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

• Drug SYS6055
  The dose will be selected based on the dose cohort, with a single administration.

Primary outcome measures

• Dose-limiting toxicities (DLTs) [Time frame: Dose-limiting toxicities (DLTs) will be assessed 28 days after the first dose.]
• Occurrence of Adverse Events (AE) and Serious Adverse Events (SAE) [Time frame: Up to 24 months after administration of 6055]
• Recommended Phase 2 Dose (RP2D) or Maximum Tolerated Dose (MTD) of SYS6055 [Time frame: through study completion, an average of 3 years]

Secondary outcome measures (12)

• Objective Response Rate (ORR) [Time frame: through study completion, an average of 3 years]
• Time to Response（TTR ） [Time frame: through study completion, an average of 3 years]
• Duration of Response (DoR) [Time frame: through study completion, an average of 3 years]
• Progression-free survival (PFS) [Time frame: through study completion, an average of 3 years]
• Overall Survival (OS) [Time frame: hrough study completion, an average of 3 years]
• PK CD19-CAR copy number and CD19 CAR-T cell content of SYS6055 [Time frame: 2 years]
• PK，CD19 CAR-T cell phenotypes [Time frame: 2 years]
• PD [Time frame: 2 years]
• PD [Time frame: 2 years]
• PD [Time frame: 2 years]
• PD [Time frame: 2 years]
• PD [Time frame: 2 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07476066 · SYS6055-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗