Relapsed or Refractory B-Cell Non-Hodgkin LymphomaPhase 1NCT06565689
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK012
A Phase 1 study testing YK012 in people with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma, run by Excyte Biopharma Ltd at 1 site in China.
Trial summary
This study aims to provide a basis for further clinical development of YK012. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
- What is being tested?
- YK012
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 9 May 2023to Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained from the patient prior to performing any study-related procedures, including screening visits.
- Males or females aged ≥ 18 to ≤ 65 years.
- Participants with an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 1.
- Participants with an estimated survival time of more than 12 weeks.
- 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.
- Participants have previously received rituximab Treatment (unless rituximab is intolerant) and at least second-line therapy.
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- 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.
- Adverse reactions caused by previous treatment have recovered to below level 1 assessed by NCI CTCAE v5.0 before screening (except hair loss).
- Participants with essentially normal function of hematology, liver, and kidney function.
- 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.
- 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.
Who cannot join
- 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.
- 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.
- 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.
- 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.
- Participants with a history or evidence of serious cardiovascular disease, including but not limited to:
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- 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).
- Known allergy to monoclonal antibody drugs or immunoglobulin.
- 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.
- 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.
- The results of serological testing for the virus are clinically significant as judged by the investigator.
- Participants with uncontrolled active infections currently require systemic anti-infective therapy, except for local treatment.
- Participants with uncontrollable space effusion (e.g. pleural effusion, abdominal effusion, pericardial effusion, etc.), as judged by the Investigator.
- Pregnant or lactating women.
- Participants with mental disorders or poor protocol compliance.
- Participants who have used live attenuated vaccines within 4 weeks prior to the first dose of YK012.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Yuankai Shi, MD, +86-13701251865, syuankaipumc@126.com
About this study
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
This study aims to provide a basis for further clinical development of YK012.
Read the 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).
- Being tested
- YK012
- Medical subject headings
- Recurrence, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YK012Drug
Also called YK012 for Injection
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
| Study group | Role | What they receive |
|---|---|---|
| YK012 | Experimental | Drug: YK012 Patients will be administered with YK012 by intravenous infusion every two weeks (Q2W, 4 weeks in a treatment cycle). Treatment will be continued until disease progression, intolerable toxicity, withdrawal of consent, patient being lost to follow-up, death or up to 6 cycles, whichever occurs first. Receives: Drug: YK012 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
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.
Measured: From the first infusion of YK012 until 28 Days after end of treatment
The incidence and profile of dose-limiting toxicity (DLT)
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).
Measured: 28 days after the first dose
The maximum tolerated dose and/or the recommended dose for further clinical trial
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.
Measured: 28 days after the first dose
Secondary outcomes (10)
Area under the concentration-time curve (AUC) after administration
Assess the AUC after treatment with YK012
Measured: 12 weeks
Maximum concentration (Cmax) after administration
Assess the Cmax after treatment with YK012
Measured: 12 weeks
Time to maximum concentration (Tmax) after administration
Assess the Tmax after treatment with YK012
Measured: 12 weeks
Terminal elimination half-life (T1/2) after administration
Assess the terminal elimination half-life (T1/2) after treatment with YK012
Measured: 12 weeks
Percentage of participants with anti-drug antibodies (ADA)
Assess the percentage of participants with ADA after treatment with YK012
Measured: 24 weeks
Tumor objective response rate (ORR)
Assess the overall response rate (ORR) after treatment with YK012
Measured: 24 weeks
Duration of response (DOR)
Assess the duration of response (DOR) after treatment with YK012
Measured: 24 weeks
Anti-lymphoma activity by progression-free survival (PFS)
Assess the progression-free survival (PFS) after treatment with YK012
Measured: 24 weeks
Number of B cells and T cells in peripheral blood after administration
Assess the number of B cells and T cells in peripheral blood after treatment with YK012
Measured: 12 weeks
Level of cytokines in peripheral blood after administration
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) .
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2024
- Study start9 May 2023
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory B-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Excyte Biopharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yuankai Shi, MD, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06565689
- Sponsor's protocol ID
- YK012-1
- Status last verified
- Jul 2026
- First submitted
- 19 Aug 2024
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06565689
- Acronym / sponsor ID
- YK012-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Excyte Biopharma LtdIndustry (pharma, biotech, devices)
- Study start
- 9 May 2023 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 22 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| YK012 | Experimental | Drug: YK012Drug: YK012 Patients will be administered with YK012 by intravenous infusion every two weeks (Q2W, 4 weeks in a treatment cycle). Treatment will be continued until disease progression, intolerable toxicity, withdrawal of consent, patient being lost to follow-up, death or up to 6 cycles, whichever occurs first. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent obtained from the patient prior to performing any study-related procedures, including screening visits.
- Males or females aged ≥ 18 to ≤ 65 years.
- Participants with an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 1.
- Participants with an estimated survival time of more than 12 weeks.
- 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.
Key exclusion criteria (17 listed)
- 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.
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YK012Also: YK012 for InjectionYK012 is a bispecific antibody targeting CD19 on B cells and CD3 on T cells leading to T cell-mediated cytotoxicity of malignant B cells | Drug | YK012 |
Primary outcome
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
Time frame: 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)
Time frame: 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
Time frame: 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.
10 secondary outcomes
Area under the concentration-time curve (AUC) after administration
Time frame: 12 weeks
Maximum concentration (Cmax) after administration
Time frame: 12 weeks
Time to maximum concentration (Tmax) after administration
Time frame: 12 weeks
Terminal elimination half-life (T1/2) after administration
Time frame: 12 weeks
Percentage of participants with anti-drug antibodies (ADA)
Time frame: 24 weeks
Tumor objective response rate (ORR)
Time frame: 24 weeks
Duration of response (DOR)
Time frame: 24 weeks
Anti-lymphoma activity by progression-free survival (PFS)
Time frame: 24 weeks
Number of B cells and T cells in peripheral blood after administration
Time frame: 12 weeks
Level of cytokines in peripheral blood after administration
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yuankai Shi, MD principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing YK012 in people with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma, run by Excyte Biopharma Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuankai Shi, MD (+86-13701251865, syuankaipumc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs) (time frame: From the first infusion of YK012 until 28 Days after end of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.