Clinical trial NCT05646758: A Clinical Trial of TQB2934 for Injection in Multiple Myeloma Subjects
Official title: A Phase I Clinical Trial Evaluating the Tolerance and Pharmacokinetics of TQB2934 for Injection in Multiple Myeloma Subjects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-12-12
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQB2934 is an anti-CD3(Early T Cell Marker)×BCMA (B cell maturation antigen) double-specific antibody，and the isoform is IgG1 (Native Immunoglobulin G1), which at one end binds to the CD3 receptor on the surface of T cells ,and the other end binds to BCMA(B cell maturation antigen) to recruit T cells around BCMA-positive cells, which can activate T cells .Active T cells release granzyme and perforin to kill BCMA-positive target cells.TQB2934 for injection is planned for the treatment of patients with multiple myeloma.


Eligibility criteria: Inclusion Criteria:

* The subjects volunteered to join the study and signed informed consent form (ICF)with good compliance;
* Age: ≥ 18 years old (when signing ICF); ECOG PS score: 0-1; The expected survival period is more than 3 months;
* Multiple myeloma with diagnostic records and meeting the IMWG diagnostic criteria;
* In the presence of measurable lesions, at least one of the following criteria must be met:

  1. Serum monoclonal immunoglobulin (M protein)≥1.0g/dL,or urine M protein≥200mg/24h;
  2. Light chain type: serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL, and the ratio of free light chain serum immunoglobulin κ and λ is abnormal;
* Relapsed or refractory multiple myeloma who have received at least 1 line of therapy in the past, and are refractory to at least 1 proteasome inhibitor (PI), 1 immunomodulator (IMiD) and 1 CD38 monoclonal antibody;
* Disease progression during or within 12 months after the last treatment (meeting the PD criteria of IMWG), including refractory or no remission of the last treatment (≥1 cycle) or disease progression within 6 months;
* Major organ function is good;
* Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; serum pregnancy/urine pregnancy test within 7 days before study enrollment;

Exclusion Criteria:

* Comorbidities and medical history:

  1. Other malignant tumors have occurred or are currently suffering from other malignant tumors within 3 years before the first medication.
  2. Unresolved toxic reactions higher than CTC AE grade 1 or higher due to any previous treatment, excluding alopecia, fatigue and peripheral neuropathy;
  3. Major surgical intervention, open biopsy, or significant traumatic injury within 28 days prior to first dose;
  4. long-term unhealed wounds or fractures;
  5. Hyperactive/venous thrombosis events occurred within 6 months before the first medication, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
  6. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
  7. Subjects with any severe and/or uncontrolled disease,include:

     1. Unsatisfactory blood pressure control (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, at least 2 measurements at intervals of more than 24 hours);
     2. Myocardial infarction, unstable angina, CTC AE ≥ grade 2 stable angina, ≥ grade 2 heart failure (New York Heart Association (NYHA) classification), ≥ grade 2 arrhythmia occurred within 6 months before the first medication;
     3. Cardiac ultrasound evaluation: left ventricular ejection fraction (LVEF) \<50%;
     4. Active or uncontrolled severe bacterial, viral or systemic fungal infection within 28 days before the first dose (≥CTC AE grade 2 infection);
     5. Hepatitis (meeting one of the following criteria: hepatitis B: HBV DNA detection value exceeds the upper limit of normal value; hepatitis C: HCV RNA detection value exceeds the upper limit of normal value) or decompensated cirrhosis (Child-Pugh grade B, C grade;
     6. Chronic obstructive pulmonary disease (COPD) and forced expiratory volume in 1 second (FEV1) \<60% of predicted value.
     7. Has developed or currently suffered from asthma within 2 years before the first medication;
     8. A history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency diseases, or a history of solid organ transplantation (except corneal transplantation), and active or autoimmune patients who need to receive systemic immunosuppressant therapy;
     9. Poorly controlled diabetes (fasting blood glucose (FBG) \>10mmol/L);
     10. Suffering from epilepsy and needing treatment;
* Tumor-related symptoms and treatment:

  1. Diagnosed with amyloidosis, plasma cell leukemia (PCL, peripheral plasma cell ratio ≥ 20%, or absolute plasma cell count ≥ 2×109/L), Waldenstrom macroglobulinemia (WM) or POEMS syndrome;
  2. Known multiple myeloma meningeal or central nervous system invasion or highly suspected meningeal or central nervous system invasion but cannot be identified;
  3. Previously received BCMA-targeted therapy;
  4. Previously received allogeneic hematopoietic stem cell transplantation or chimeric antigen receptor T (CAR-T), CAR-NK cell therapy; or received autologous hematopoietic stem cell transplantation (ASCT) within 12 weeks before the first drug;
  5. Received targeted therapy, cytotoxic drugs or any antibody therapy within 3 weeks before the first medication; received proteasome inhibitor therapy or radiotherapy within 2 weeks before the first medication; received immunomodulator therapy within 1 week before the first medication.(Prophylaxis to prevent infusion-related reactions prior to study drug administration)(Calculate the washout period from the end of the last treatment);
* research treatment related:

  1. History of live attenuated vaccine vaccination within 28 days before the first dose or planned live attenuated live vaccine vaccination during the study;
  2. Unexplained severe allergy history, known allergy to monoclonal antibody drugs or exogenous human immunoglobulin, or known allergy to TQB2934 for injection or excipients in pharmaceutical preparations;
* Those who have participated in other anti-tumor drug clinical trials within 4 weeks before the first drug use or have not exceeded 5 drug half-lives;
* According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are considered unsuitable for enrollment for other reasons;

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 18 months
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 18 months
measure: Incidence and severity of serious adverse events (AEs)
timeFrame: Up to 18 months
measure: Incidence and severity of adverse events (AEs)
timeFrame: Up to 18 months
measure: Incidence and severity abnormal laboratory test value
timeFrame: Up to 18 months
Secondary outcomes:
measure: Elimination half-life (t1/2)
timeFrame: 120 hours after administration
measure: Area under the plasma concentration-time curve (AUC0-last)
timeFrame: 120 hours after administration
measure: Apparent clearance (CL)
timeFrame: 120 hours after administration
measure: Terminal phase apparent volume of distribution (Vz)
timeFrame: 120 hours after administration
measure: Plasma trough concentration (Cmin)
timeFrame: 120 hours after administration
measure: Overall response rate (ORR)
timeFrame: Up to 18 months
measure: Clinical benefit rate (CBR)
timeFrame: Up to 18 months
measure: Very good partial response rate (VGPR)
timeFrame: Up to 18 months
measure: Complete Response (CR) / Strict Complete Response (sCR) Rate
timeFrame: Up to 18 months
measure: Negative rate of minimal residual disease (MRD)
timeFrame: Up to 18 months
measure: Duration of remission (DOR)
timeFrame: Up to 18 months
measure: Time to first remission (TTR)
timeFrame: Up to 18 months
measure: Progression-free survival (PFS)
timeFrame: Up to 18 months
measure: Overall survival (OS)
timeFrame: Up to 18 months
measure: Disease status was determined using the International Myeloma Working Group (IMWG) 2016 criteria
timeFrame: Up to 18 months
measure: Antidrug antibody (ADA) incidence
timeFrame: Up to 18 months
measure: Peripheral blood soluble BCMA (sBCMA) level
timeFrame: Up to 18 months
measure: Receptor occupancy rate (RO)
timeFrame: Up to 18 months
measure: Cytokine Interleukin 2 (IL-2) levels
timeFrame: Up to 18 months
measure: Cytokine Interleukin 6 (IL-6) levels
timeFrame: Up to 18 months
measure: Cytokine Interleukin 10 (IL-10) levels
timeFrame: Up to 18 months
measure: Cytokine Interferon γ (IFN-γ) levels
timeFrame: Up to 18 months
measure: Cytokine Interferon α (IFN-α) levels
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Canter
state: Guangdong
city: Zhengzhou
country: China
facility: The Henan Cancer Hospital
state: Henan
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Jinan
country: China
facility: Shandong First Medical University Affiliated Tumor Hospital
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital of Fudan University
state: Shanghai
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: