Study of YK012 in B-cell Acute Lymphoblastic Leukemia

An Open-Label, Multi-Center, Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of YK012 in Participants With B-cell Acute Lymphoblastic Leukemia

The purpose of this study is to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of YK012 administered as monotherapy in participants with B-cell acute lymphoblastic leukemia (B-ALL).

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: YK012

Detailed Description

YK012 is a bispecific antibody designed to link B cells and T cells resulting in T-cell activation and a cytotoxic T-cell response against cluster of differentiation (CD)19 expressing cells. Relapsed/refractory B-ALL in adult patients is an aggressive malignant disease with dismal prognosis. This study is designed in 2 parts as described below: Phase Ib (dose escalation) and Phase II (dose expansion). If in Phase Ib it is observed in adult subjects at doses with manageable risk and antitumor activity, studies in pediatric subjects can be initiated to explore safety and efficacy in pediatric subjects, as well as pharmacokinetic profiles.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jie Jin, MD; Phone Number: +86-0571-87236898; Email: jiej0503@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yang Liang, MD
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Peilong Lai, MD
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-Sen Memorial Hospital
      • Contact: Danian Nie
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • Recruiting
      • The Affiliated Hospital of Guizhou Medical University
      • Contact: Jishi Wang, MD
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Provincial People's Hospital
      • Contact: Zunmin Zhu, MD
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Zhenyu Li, MD
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Fei Li, MD
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Sujun Gao, MD
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Recruiting
      • Affiliated Zhongshan Hospital of Dalian University
      • Contact: Xiang Li
      • Contact: Meiyun Fang, MD
    • Shenyang, Liaoning, China, 110000
      • Recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Wei Yang, MD
  • Yunnan
    • Kunming, Yunnan, China, 650033
      • Recruiting
      • The Second Affiliated Hospital of Kunming Medical University
      • Contact: Zeping Zhou, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Jie Jin, MD; Phone Number: +86-0571-87236898; Email: jiej0503@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants or their legally acceptable representative must sign an ICF indicating that the participants understand the purpose of, and procedures required for the study and are willing to participate in the study.
2. Eastern Cooperative Oncology Group Performance Status (ECOG) of 0-2.
3. An estimated survival time of more than 12 weeks.

4. A definitive diagnosis of CD19-positive B-cell acute lymphoblastic leukemia with any of the following conditions:

   1. Ph-negative B-ALL with any of the following: i. Failure to achieve complete remission after initial induction therapy. ii. Failure to achieve complete remission after salvage treatment. iii. Relapse with first remission duration ≤12 months. iv. Second or later relapse. v. Relapse after hematopoietic stem cell transplantation (HSCT).
   2. Ph-positive B-ALL: failure to 1 or more tyrosine kinase inhibitors (TKIs), or intolerance to treatment with TKIs, or with the T315I mutation.
5. ≥ 5% blasts in the bone marrow by morphologic assessment.
6. Recovery to Grade 0-1 (Graded by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0) from adverse events related to prior therapy except alopecia.
7. Adequate hematological and organ function.
8. Female participants of childbearing potential must have a negative serum pregnancy test at screening. Female patients who are sexually active must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
9. 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 3 months after the last dose.

Exclusion Criteria:

1. Burkitt´s Leukemia according to World Health Organization (WHO) classification.

2. History of antitumor therapy as follows, before the first dose of study drug:

   1. Targeted therapy with small molecule drug within 2 weeks or 5 half-lives, whichever is longer
   2. Targeted therapy with macromolecular drug or Immunomodulatory agent therapy within 3 weeks
   3. Radiotherapy or chemotherapy (except for intrathecal chemotherapy and dexamethasone), or treatment with Chinese traditional/patent medicine that has definite antitumor effect within 2 weeks
   4. Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is shorter
   5. Receipt of any live attenuated vaccines or live virus vaccine within 4 weeks
   6. Autologous stem cell transplantation within 6 weeks
   7. History of organ transplant, or allogeneic stem cell transplantation within 12 weeks.
3. Any active acute graft-versus-host disease (GvHD), grade 2-4 (according to Glucksberg criteria) or active chronic GvHD requiring systemic treatment.
4. Other malignancy within 5 years, except localized malignancies that have been adequately treated or free of the disease for ≥ 5 years, e.g., basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-muscle invasive bladder cancer, localized prostate cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast.
5. Active central nervous system (CNS) involvement or meningeal involvement with clinical signs, or other evidence of uncontrolled metastases to the CNS or meninges, judged by the investigator.
6. 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.

7. History or evidence of cardiovascular disease, including:

   1. Acute coronary syndromes (e.g., myocardial infarction, unstable angina)
   2. Coronary angioplasty or stenting within 6 months prior to enrollment
   3. Clinically significant unstable arrhythmias (e.g., atrial fibrillation), however, atrial fibrillation has been controlled for over 30 days prior to the first dose of YK012 were allowed
   4. New York Heart Association (NYHA) stage III or higher congestive heart failure
   5. Left ventricular ejection fraction (LVEF) below lower limit of the study center, or LVEF<50% if there is no lower limit at the study center
   6. The Fridericia-corrected QT interval (QTcF, mean of triplicate measurements) ≥ 470 msec (female) or ≥ 450 msec (male)
   7. Implantable defibrillator
   8. Clinically uncontrollable hypertension (i.e., SBP≥160 mm Hg and/or DBP≥100 mm Hg).
8. Known allergy to monoclonal antibody drugs or exogenous immunoglobulin.
9. History of CD19 targeted therapy and positive test result for immunogenicity of YK012 at screening.
10. 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 to Grade ≤1 or baseline graded by CTCAE v5.0 before the first dose of the YK012.
11. Regular dose of systemic corticosteroids during 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 immunosuppressive therapy within 4 weeks prior to study entry.
12. Virological tests: Hepatitis B virus surface antigen (HBsAg) positive and/or hepatitis B core antibody (HBcAb) positive, and hepatitis B virus (HBV) deoxyribonucleic acid (DNA)>ULN of the testing agency; Hepatitis C antibody (HCV-Ab) positive and hepatitis C virus-RNA (HCV-RNA)>ULN of the testing agency; Anti-human immunodeficiency virus (Anti-HIV) positive. Participants will be excluded from the study if any of the above criteria is met.
13. Uncontrolled active infections requiring oral or intravenous systemic therapy, except for local treatment.
14. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently).
15. Pregnant or lactating women.
16. Known mental disorder that may affect study compliance or poor compliance.
17. Other serious systemic diseases or laboratory abnormalities or other reasons that the investigator believes are not appropriate for participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YK012; Participants will be assigned to a dose level of YK012 based on when the participants join this study. Participants will receive YK012 by intravenous infusion (IV), once per week, four weeks per treatment cycle.	Drug: YK012; The treatments include 2 cycles of induction treatment, 3 cycles of consolidation treatment, and up to 5 cycles of maintenance treatment.; Other Names: YK012 for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 related to the IMP (Investigational Medicinal Product). This outcome measure is applicable for dose escalation phase only. The MTD dose will be calculated by the statistician upon completion of the dose escalation study.	28 days after the first dose
Maximum Tolerated dose (MTD) or The Recommended Dose for Future Clinical Study	This outcome measure is applicable for dose escalation phase only. The MTD dose will be calculated by the statistician upon completion of the dose escalation study.	Through study completion, 20 weeks
Number of Participants with Adverse Events	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.	From the time the participant signs the ICF until the end of the safety visit period, assessed up to 24weeks.
Number of Participants with Serious Adverse Events	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 IMP, and congenital abnormalities or birth defects.	From the time the participant signs the ICF until the end of the safety visit period, assessed up to 24weeks.
Dose Expansion Phase: Objective Response Rate (ORR)	ORR is defined as percentage of participants achieving either a complete response (CR) or complete remission with partial hematological recovery (CRi). The MTD dose will be calculated by the statistician upon completion of the dose escalation study. This outcome measure is applicable for dose expansion phase only.	From the time the participant signs the ICF until hematological relapse, assessed up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve (AUC)	The PK (AUC) of YK012 will be evaluated.	Up to 20 weeks
Maximum Observed Concentration (Cmax)	The PK (Cmax) of YK012 will be evaluated.	Up to 20 weeks
Time to Reach Maximum Concentration (Tmax)	The PK (Tmax) of YK012 will be evaluated.	Up to 20 weeks
Half Life (t1/2) of YK012	The PK (t1/2) of YK012 will be evaluated.	Up to 20 weeks
Clearance (CL) of YK012	The PK (CL) of YK012 will be evaluated.	Up to 20 weeks
Trough Plasma Concentration (Ctrough)	The PK (Ctrough) of YK012 will be evaluated.	Up to 20 weeks
Percentage of Participants with Anti-Drug Antibody (ADA) and Neutralizing Antibody (Nab) Against YK012	Assess the percentage of participants with ADA and Nab (only assessed when ADA positive except for the screening period) after treatment with YK012.	Up to 20 weeks
Dose Escalation Phase: Objective Response Rate (ORR)	ORR is defined as percentage of participants achieving either a complete response (CR) or complete remission with partial hematological recovery (CRi). The MTD dose will be calculated by the statistician upon completion of the dose escalation study. This outcome measure is applicable for dose escalation phase only.	From the time the participant signs the ICF until hematological relapse, assessed up to 1 year
Relapse-free Survival (RFS)	RFS was measured from first dose of YK012 until the first assessment of documented relapse, or death due to any cause, whichever occurs first including the time after the transplant.	From the time the participant signs the ICF until hematological relapse, assessed up to 1 year
Overall survival (OS)	Overall survival was measured from the first treatment with YK012 until death due to any cause. Participants who did not die were censored at their last contact date.	From the date of first dose until loss of follow-up, death, withdrawal of informed consent, or the end of study, whichever occurs first, assessed up to 1 year.
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	Up to 20 weeks

Collaborators and Investigators

• Sponsor: Excyte Biopharma Ltd
• Investigators: Principal Investigator: Jie Jin, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: August 28, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Burkitt Lymphoma; Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: YK012-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No