Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Conditions
Brief summary
This study aims to provide a basis for further clinical development of YK012.
Detailed description
This study is the first-in-human clinical trial to evaluate the safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy of YK012 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL).
Interventions
DRUGYK012
YK012 is a bispecific antibody targeting CD19 on B cells and CD3 on T cells leading to T cell-mediated cytotoxicity of malignant B cells
Sponsors
Excyte Biopharma Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained from the patient prior to performing any study-related procedures, including screening visits. 2. Males or females aged ≥ 18 to ≤ 65 years. 3. Participants with an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 1. 4. Participants with an estimated survival time of more than 12 weeks. 5. Participants with relapsed or refractory B-NHL. These patients' disease history must meet the following World Health Organization (WHO) diagnostic subtypes of B-NHL : follicular lymphoma (FL), MALT lymphoma, lymphoplasmacytic lymphoma (LPL), mantle cell lymphoma (MCL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), grey zone lymphoma, Burkitt lymphoma. 6. Participants have previously received rituximab Treatment (unless rituximab is intolerant) and at least second-line therapy. 7. Participants with at least one evaluable tumor lesion per the Lugano 2014 criteria, i.e., a lymph node lesion \> 15 mm in long diameter or an extranodal lesion \> 10 mm in long diameter according to computed tomography (CT) cross-sectional imaging. 8. Adverse reactions caused by previous treatment have recovered to below level 1 assessed by NCI CTCAE v5.0 before screening (except hair loss). 9. Participants with essentially normal function of hematology, liver, and kidney function. 10. Female participants of childbearing potential must have a negative blood pregnancy test and agree to use reliable methods of contraception (hormonal or barrier methods or sexual abstinence) with their partner throughout the study period and until 3 months after the last dose. 11. Male participants must agree to use reliable methods of contraception (barrier methods or sexual abstinence) and avoid sperm donation throughout the study period and until 90 days after the last dose.
Exclusion criteria
1. Participants who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs) | From the first infusion of YK012 until 28 Days after end of treatment | An AE is defined as any untoward medical event that occurs after a subject receives the investigational drug, which may be manifested as symptoms, signs, diseases, or laboratory abnormalities, but may not necessarily have a causal relationship with the investigational drug. An SAE refers to an untoward medical occurrence such as death, life-threatening event, permanent or serious disability or loss of function, need for hospitalization or prolongation of hospitalization after the subject receives the investigational drug, and congenital abnormalities or birth defects. |
| The incidence and profile of dose-limiting toxicity (DLT) | 28 days after the first dose | The toxicities occurring within 28 days (i.e., DLT observation period) after the first dose will be defined as DLTs in the discretion of the investigator as possibly, probably, or definitely related to the IMP (Investigational Medicinal Product). |
| The maximum tolerated dose and/or the recommended dose for further clinical trial | 28 days after the first dose | The MTD will be determined based on the occurrence rate of the DLT. The MTD is defined as the highest dose in which 1/6 or less subjects experience a DLT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve (AUC) after administration | 12 weeks | Assess the AUC after treatment with YK012 |
| Maximum concentration (Cmax) after administration | 12 weeks | Assess the Cmax after treatment with YK012 |
| Time to maximum concentration (Tmax) after administration | 12 weeks | Assess the Tmax after treatment with YK012 |
| Terminal elimination half-life (T1/2) after administration | 12 weeks | Assess the terminal elimination half-life (T1/2) after treatment with YK012 |
| Percentage of participants with anti-drug antibodies (ADA) | 24 weeks | Assess the percentage of participants with ADA after treatment with YK012 |
| Tumor objective response rate (ORR) | 24 weeks | Assess the overall response rate (ORR) after treatment with YK012 |
| Duration of response (DOR) | 24 weeks | Assess the duration of response (DOR) after treatment with YK012 |
| Anti-lymphoma activity by progression-free survival (PFS) | 24 weeks | Assess the progression-free survival (PFS) after treatment with YK012 |
| Number of B cells and T cells in peripheral blood after administration | 12 weeks | Assess the number of B cells and T cells in peripheral blood after treatment with YK012 |
| Level of cytokines in peripheral blood after administration | 12 weeks | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interferon gamma (IFN-ɣ), interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor-alpha (TNF-α) . |
Countries
China
Contacts
CONTACTYuankai Shi, MD
PRINCIPAL_INVESTIGATORYuankai Shi, MD
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed