Relapsed or Refractory Multiple Myeloma (RRMM)
Conditions
Keywords
Relapsed or Refractory Multiple Myeloma, Bispecific Antibodies, YKST02, BCMA, CD3
Brief summary
The goal of this Phase 2 clinical trial is to learn whether YKST02 is effective and safe in adults with relapsed or refractory multiple myeloma. The study will also evaluate how YKST02 is processed by the body (pharmacokinetics), how it affects the body (pharmacodynamics), and whether it causes the body to produce anti-drug antibodies. The main questions it aims to answer are: Does YKST02 demonstrate clinical efficacy in adults with relapsed or refractory multiple myeloma? What side effects occur during treatment with YKST02? What are the pharmacokinetic, pharmacodynamic, and immunogenicity characteristics of YKST02? Participants will: Complete screening assessments to determine whether they are eligible for the study. Receive YKST02 by intravenous infusion according to the study treatment schedule. Undergo regular assessments to evaluate treatment response and monitor safety. Provide blood and urine samples for pharmacokinetic, pharmacodynamic, and immunogenicity testing. Complete follow-up visits after treatment discontinuation to monitor disease progression and survival. Multiple myeloma is a cancer of plasma cells that remains incurable despite advances in treatment. Although currently available therapies can improve outcomes, most patients eventually experience disease relapse or become refractory to treatment. YKST02 is an investigational humanized bispecific antibody targeting BCMA on myeloma cells and CD3 on T cells. Simultaneous binding to BCMA and CD3 may activate T cells and promote tumor cell killing. This is a multicenter, open-label study consisting of two parts (Phase IIa and Phase IIb). In Phase IIa, participants will initially receive YKST02 at the starting dose level. Safety and efficacy data from this part of the study will be reviewed to determine the dose to be evaluated in Phase IIb.
Detailed description
Relapsed or refractory multiple myeloma (RRMM) remains an incurable plasma cell malignancy despite substantial advances in treatment. Although currently available therapies, including proteasome inhibitors, immunomodulatory agents, anti-CD38 monoclonal antibodies, autologous stem cell transplantation, and B-cell maturation antigen (BCMA)-targeted therapies, have improved clinical outcomes, most patients eventually experience disease progression or relapse. Therefore, additional treatment options remain needed. BCMA is highly expressed on malignant plasma cells and has emerged as an important therapeutic target for multiple myeloma. YKST02 is an investigational humanized bispecific antibody targeting BCMA on myeloma cells and CD3 on T cells. Through simultaneous binding to BCMA and CD3, YKST02 is intended to redirect T cells to BCMA-expressing tumor cells, resulting in T-cell activation and tumor cell killing. This is a multicenter, open-label, Phase 2 study designed to evaluate the efficacy, safety, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of YKST02 in adults with relapsed or refractory multiple myeloma. Approximately 39 to 64 participants will be enrolled across multiple study centers in China, depending on the number of dose cohorts evaluated in Phase IIa. The study consists of two parts. Phase IIa is designed to evaluate the safety and efficacy of YKST02 and to support selection of the dose for further evaluation in Phase IIb. Phase IIb will further evaluate the efficacy, safety, pharmacokinetics, immunogenicity, and pharmacodynamics of YKST02 at the selected dose. Participants who meet all eligibility criteria will receive YKST02 according to the protocol-defined treatment schedule and undergo regular efficacy and safety assessments throughout the study. Blood and urine samples will be collected for pharmacokinetic, pharmacodynamic, and immunogenicity evaluations. Participants will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, completion of the protocol-defined treatment period, or another protocol-defined discontinuation criterion. After treatment discontinuation, participants will enter follow-up for disease progression and survival.
Interventions
DRUGYKST02
Participants will receive YKST02 by intravenous infusion according to the protocol-defined treatment schedule. Treatment will continue until a protocol-defined treatment discontinuation criterion is met.
Sponsors
Excyte Biopharma Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Able and willing to provide written informed consent (or consent provided by a legally authorized representative, where applicable) and comply with all study procedures. * Diagnosis of multiple myeloma according to the 2016 International Myeloma Working Group (IMWG) diagnostic criteria. * Relapsed or refractory multiple myeloma after at least two prior lines of therapy, including prior exposure to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. * Measurable disease as defined in the study protocol. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Estimated life expectancy of at least 12 weeks. * Recovery from clinically significant toxicities related to prior anticancer therapy to an acceptable level before study treatment (except alopecia). * Adequate hematologic, hepatic, renal, and coagulation function based on protocol-specified laboratory criteria. * Women of childbearing potential must have a negative pregnancy test before study treatment and agree to use effective contraception during the study and for 3 months after the last dose of study treatment. * Male participants must agree to use effective contraception during the study and for 3 months after the last dose of study treatment and must not donate sperm during this period.
Exclusion criteria
* Plasma cell leukemia, Waldenström macroglobulinemia, POEMS syndrome, or primary light-chain (AL) amyloidosis. * Prior treatment with any BCMA-targeted therapy, including BCMA-directed chimeric antigen receptor (CAR) T-cell therapy. * Recent anticancer therapy, investigational medicinal product, radiotherapy, stem cell transplantation, or organ transplantation that does not meet the protocol-defined washout requirements. * Active graft-versus-host disease (GvHD) requiring systemic treatment or clinically significant active GvHD. * History of another malignancy within the past 5 years, except for adequately treated malignancies with negligible risk of recurrence, as specified in the protocol. * Symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or evidence of uncontrolled CNS or leptomeningeal involvement that, in the investigator's judgment, makes the participant unsuitable for study participation. * History of clinically significant central nervous system disorders that may increase study risk or interfere with study participation. * Clinically significant cardiovascular disease, including recent acute coronary syndrome or coronary revascularization, uncontrolled arrhythmias, New York Heart Association (NYHA) Class III or IV heart failure, clinically significant cardiac dysfunction, prolonged QT interval, or uncontrolled hypertension. * Known hypersensitivity to monoclonal antibodies, human immunoglobulins, or any component of the study drug. * Major surgery or severe trauma shortly before study treatment, or planned major surgery during the study. * Requirement for systemic corticosteroids or other immunosuppressive therapy for conditions other than multiple myeloma that does not meet protocol requirements. * Active hepatitis B or hepatitis C infection, positive human immunodeficiency virus (HIV) test, or other clinically significant uncontrolled infection requiring systemic therapy. * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. * Pregnant or breastfeeding women. * Known psychiatric illness or other conditions that may compromise the participant's ability to comply with study requirements. * Receipt of a live or live attenuated vaccine within the protocol-defined period before the first dose of study treatment. * Any other clinically significant medical condition, laboratory abnormality, or circumstance that, in the investigator's judgment, would make participation in the study inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From first dose until disease progression or initiation of subsequent anti-cancer therapy, whichever occurs first (up to approximately 2 years). | Overall response rate (ORR), defined as the proportion of participants achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by the investigator according to the 2016 International Myeloma Working Group (IMWG) response criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | From first dose until first documented response (up to approximately 2 years) | Time from the first dose of YKST02 to the first documented objective response (partial response or better) according to the 2016 International Myeloma Working Group (IMWG) response criteria. |
| Progression-Free Survival (PFS) | From first dose until disease progression, death, or end of study (up to approximately 2 years) | Time from the date of the first dose of YKST02 to the first documented disease progression or death from any cause, whichever occurs first, according to the 2016 IMWG response criteria. |
| Duration of Response (DOR) | From first documented response until disease progression, death, or end of study (up to approximately 2 years) | Time from the first documented objective response to the first documented disease progression or death from any cause, whichever occurs first, according to the 2016 IMWG response criteria. |
| Overall Survival (OS) | From the date of first dose until death from any cause or study completion | Time from the date of the first dose of YKST02 to death from any cause. Participants without documented death will be censored at the earlier of the last date known to be alive or the study cutoff date. |
| Minimal Residual Disease (MRD) Negativity Rate | From first dose through 28 days after the last dose (up to approximately 2 years) | Proportion of participants who achieve minimal residual disease (MRD) negativity. MRD assessment will be performed in participants who achieve complete response (CR) or better. |
| Number of Participants with Adverse Events (AEs) | From the first dose through 28 days after the last dose (up to approximately 2 years). | An adverse event (AE) is any untoward medical occurrence in a participant administered the investigational product. An AE may be manifested as a sign, symptom, disease, or abnormal laboratory finding and does not necessarily have a causal relationship with the investigational product. |
| Number of Participants with Serious Adverse Events (SAEs) | From the first dose through 28 days after the last dose (up to approximately 2 years). | A serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is considered an important medical event. |
| Number of Participants with Clinically Significant Laboratory Abnormalities | From first dose through 28 days after the last dose (up to approximately 2 years) | Number of participants with treatment-emergent clinically significant laboratory abnormalities, as assessed by the investigator. |
| Eastern Cooperative Oncology Group (ECOG) performance status | From first dose through 28 days after the last dose (up to approximately 2 years) | Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance status, assessed using the ECOG Performance Status scale (scores range from 0 to 5, with lower scores indicating better functional status). |
| Incidence of Anti-drug Antibodies (ADA) | From first dose through 28 days after the last dose (up to approximately 2 years) | Proportion of participants who develop anti-drug antibodies (ADA) following administration of YKST02. |
| Incidence of Neutralizing Antibodies (NAb) | From first dose through 28 days after the last dose (up to approximately 2 years) | Proportion of ADA-positive participants who develop neutralizing antibodies (NAb). |
| Area Under the Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) | From first dose through end of PK sampling (up to approximately 2 years) | Area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) of YKST02. |
| Maximum Observed Serum Concentration (Cmax) | From first dose through end of PK sampling (up to approximately 2 years) | Maximum observed serum concentration (Cmax) of YKST02 following study drug administration. |
| Time to Maximum Serum Concentration (Tmax) | From first dose through end of PK sampling (up to approximately 2 years) | Time to maximum observed serum concentration (Tmax) of YKST02 following study drug administration. |
| Terminal Elimination Half-life (t½) | From first dose through end of PK sampling (up to approximately 2 years) | Terminal elimination half-life (t½) of YKST02 estimated using noncompartmental pharmacokinetic analysis. |
Countries
China
Contacts
CONTACTWenming Chen, MD
Outcome results
None listed