Clinical trial NCT06565689: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK012
Official title: A Multi-center, Open-Label, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK012 in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Lead sponsor: Excyte Biopharma Ltd
Sponsor class: INDUSTRY
First posted: 2024-08-22
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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 exclusion criteria will not be included in this study:

   Treatment with biologic targeted therapy or anti-tumor immunotherapy within 4 weeks prior to the first dose of YK012; Participants who have received chemotherapy within 4 weeks prior to the first dose of YK012; Participants who have received small molecule targeted agents within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of YK012; Participants who have received other investigational agents within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of YK012; Participants who have received radical/extensive radiotherapy within 4 weeks prior to the first dose of YK012, or local palliative radiotherapy within 2 weeks prior to the first dose of YK012, or acute toxicity induced by previous radiotherapy have not recovered to grade ≤1; Participants who have received autologous HSCT within 12 weeks prior to the first dose of YK012; Participants who have received allogeneic HSCT or organ transplant; Participants who have received chimeric antigen receptor T cell (CAR-T) immunotherapy.
2. History of malignancy other than B-cell NHL within 5 years prior to study entry, except for local cancers that have been clearly cured or have been free of disease for at least 5 consecutive years.
3. Participants with clinically symptomatic metastases to the central nervous system or meninges, or other evidence of uncontrolled metastases to the CNS or meninges, judged by the Investigator.
4. a) History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis; b) Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI.
5. Participants with a history or evidence of serious cardiovascular disease, including but not limited to:

   Acute coronary; Coronary angioplasty or stent implantation within 6 months prior to first dose of YK012; Clinically significant unstable arrhythmias (e.g., atrial fibrillation) , however, whose atrial fibrillation have been controlled for over 30 days prior to the first dose of YK012 were allowed to be enrolled; Severe cardiac rhythm abnormalities; Grade III or higher congestive heart failure as defined by the New York Heart Association (NYHA) standards; Cardiac valve morphological abnormalities recorded by ECHO (≥ grade 2), those participants with grade 1 cardiac valve morphological abnormalities (such as mild regurgitation/stenosis) were allowed to be enrolled, but participants with moderate valve thickening were excluded; Left ventricular ejection fraction (LVEF) below lower limit of the study center, or LVEF\<50% if there is no lower limit at the research center; QTcF ≥ 470 msec (female) or ≥ 450 msec (male)； Implantable defibrillator; Participants with clinically uncontrollable hypertension (i.e., SBP≥160 mm Hg and/or DBP≥100 mm Hg).
6. Known allergy to monoclonal antibody drugs or immunoglobulin.
7. Participants who have undergone any major organ surgery or significant trauma within 4 weeks prior to the first dose of YK012, or those requiring elective surgeries during the study, and all AEs associated with surgery or significant trauma have not recovered before the first dose of the YK012.
8. Regular dose of systemic corticosteroids during the 4 weeks prior to initiation of study drug or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent during the trial, or any other systemic immunosuppressive therapy within 4 weeks prior to study entry.
9. The results of serological testing for the virus are clinically significant as judged by the investigator.
10. Participants with uncontrolled active infections currently require systemic anti-infective therapy, except for local treatment.
11. Participants with uncontrollable space effusion (e.g. pleural effusion, abdominal effusion, pericardial effusion, etc.), as judged by the Investigator.
12. Pregnant or lactating women.
13. Participants with mental disorders or poor protocol compliance.
14. Participants who have used live attenuated vaccines within 4 weeks prior to the first dose of YK012.
15. Participants with any other condition or circumstance that would, in the discretion of the Investigator, make the subject unsuitable for participation in this clinical study.

Primary outcomes:
measure: Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
timeFrame: From the first infusion of YK012 until 28 Days after end of treatment
measure: The incidence and profile of dose-limiting toxicity (DLT)
timeFrame: 28 days after the first dose
measure: The maximum tolerated dose and/or the recommended dose for further clinical trial
timeFrame: 28 days after the first dose
Secondary outcomes:
measure: Area under the concentration-time curve (AUC) after administration
timeFrame: 12 weeks
measure: Maximum concentration (Cmax) after administration
timeFrame: 12 weeks
measure: Time to maximum concentration (Tmax) after administration
timeFrame: 12 weeks
measure: Terminal elimination half-life (T1/2) after administration
timeFrame: 12 weeks
measure: Percentage of participants with anti-drug antibodies (ADA)
timeFrame: 24 weeks
measure: Tumor objective response rate (ORR)
timeFrame: 24 weeks
measure: Duration of response (DOR)
timeFrame: 24 weeks
measure: Anti-lymphoma activity by progression-free survival (PFS)
timeFrame: 24 weeks
measure: Number of B cells and T cells in peripheral blood after administration
timeFrame: 12 weeks
measure: Level of cytokines in peripheral blood after administration
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, MD
role: PRINCIPAL_INVESTIGATOR
References: