Clinical Study of TQB2934 Injection in Relapsed/Refractory Multiple Myeloma

Official title

A Randomized, Open-Label, Multicenter Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQB2934 Injection Versus Investigator-Selected Regimens in Patients With Relapsed/Refractory Multiple Myeloma

Overview

This study is a randomized, open-label, multicenter Phase III clinical trial involving patients with relapsed/refractory multiple myeloma. The estimated total sample size is 260 cases, who will be randomly assigned in a 1:1 ratio to the test group and the control group. The primary objective of the study is to demonstrate the efficacy of TQB2934 for injection compared to the investigator-selected regimen in subjects with relapsed or refractory multiple myeloma (RRMM) by evaluating progression-free survival (PFS).

Interventions

• Drug TQB2934 injection
  TQB2934 injection is a bispecific antibody targeting B-cell maturation antigen (BCMA) and Cluster of Differentiation 3 (CD3).
• Drug Pomalidomide Capsule
  Pomalidomide capsules are an immunomodulatory(IMiD).
• Drug Selinexor tablets
  Selinexor is a selective nuclear export protein inhibitor.
• Drug Dexamethasone tablets
  Dexamethasone tablets are a type of adrenocortical hormone drug.

Primary outcome measures

• Progression-free survival (PFS) [Time frame: Baseline up to 5 years]

Secondary outcome measures (12)

• Investigator-assessed PFS [Time frame: Baseline up to 5 years]
• PFS rates at 6, 12 and 18 months [Time frame: From baseline to 18 months]
• Overall response rate (ORR) [Time frame: Baseline up to 5 years]
• Very Good Partial Response (VGPR) [Time frame: Baseline up to 5 years]
• Complete Response (CR) Rate [Time frame: Baseline up to 5 years]
• Duration of remission (DOR) [Time frame: Baseline up to 5 years]
• Time to first remission (TTR) [Time frame: Baseline up to 5 years]
• Negative rate of minimal residual disease (MRD) [Time frame: Baseline up to 5 years]
• Overall survival (OS) [Time frame: From randomization to death, the estimated evaluation period is up to 5 years]
• Adverse event rate [Time frame: From randomization to 2 months after the last dose]
• Peak concentration (Cmax) [Time frame: Before Pre-dose, before dose of Cycle 1 Day 1, Cycle 2 Day 1, Cycle 6 Day 1, Cycle 12 Day 1, after dose of Cycle 2 Day 1, Cycle 6 Day 1，Last visit (up to 5 years), each cycle is 28 days.]
• Anti-drug antibody (ADA) positive rate [Time frame: Before Pre-dose, before dose of Cycle 1 Day 1, Cycle 2 Day 1, Cycle 6 Day 1, Cycle 12 Day 1, Last visit (up to 5 years) and 30 days after the last administration each, each cycle is 28 days.]

Eligibility criteria

Inclusion criteria

• Voluntarily join this study, sign the Informed Consent Form (ICF), and demonstrate good compliance.
• Aged 18 to 75 years old (as of the date of signing the ICF); gender not limited; Eastern Cooperative Oncology Group Performance Status (ECOG) of 0-2.
• Expected survival greater than 3 months.
• Patients with relapsed or refractory multiple myeloma.
• During or after the most recent treatment, there is evidence of disease progression or failure to achieve remission after the last line of treatment。
• Measurable disease at screening.
• Adequate organ function as indicated by laboratory tests meeting the criteria.
• Women of childbearing potential must agree to use effective contraception during the study and for 12 months after the last dose of study treatment, and agree not to donate eggs for reproduction during this period. Must not be breastfeeding and must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Men who have not had a vasectomy and their female partners of childbearing potential should also agree to use effective contraception during the study and for 12 months after the last dose of study treatment, and agree not to donate sperm during this period.

Exclusion criteria

• History of other malignancies within 5 years prior to informed consent or concurrent presence of other malignancies. The following exceptions are allowed: other malignancies cured by surgery alone with a disease-free survival (DFS) ≥5 years; cured carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)\].
• Diagnosis of plasma cell leukemia (defined as circulating plasma cells ≥5% in peripheral blood according to standard classification), Waldenström macroglobulinemia, primary light-chain (AL) amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M protein\], and skin changes), or solitary plasmacytoma.
• History of prior anticancer treatment, including but not limited to:

• Receipt of chimeric antigen receptor T-cell (CAR-T), Chimeric Antigen Receptor T-Cell Immunotherapy(CAR-T), Chimeric Antigen Receptor Natural Killer Cells (CAR-NK), or other cellular therapies within 3 months prior to randomization;
• Receipt of autologous stem cell transplantation within 3 months prior to randomization;
• Receipt of allogeneic stem cell transplantation within 6 months prior to randomization; subjects must have discontinued all immunosuppressive therapy for ≥6 weeks and have no signs or symptoms of graft-versus-host disease (GVHD);
• Receipt of molecular targeted therapy, investigational drugs, or invasive investigational medical devices within 3 weeks or 5 drug half-lives (whichever is shorter) prior to randomization;
• Receipt of monoclonal antibodies, bispecific antibodies, chemotherapy, etc., within 3 weeks prior to randomization;
• Receipt of proteasome inhibitors (PI), immunomodulatory drugs (IMiDs), localized radiotherapy, palliative radiotherapy, or Chinese patent medicines with antitumor indications approved by the National Medical Products Administration (NMPA) within 2 weeks prior to randomization.
• Previously refractory to control group drugs, or with contraindications, life-threatening allergic reactions, or intolerance to previous treatments.
• Receipt of systemic corticosteroids at a cumulative dose ≥140 mg prednisone (or equivalent) within 2 weeks prior to randomization. Topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids are excluded from the cumulative dose calculation (see Appendix for dose conversion).
• Toxicities from prior antitumor therapy have not recovered to baseline or ≤ Grade 1, except for Grade 2 alopecia, non-clinically significant and asymptomatic laboratory abnormalities, and hypothyroidism stabilized by hormone replacement therapy, as judged by the investigator to pose no safety risk.
• History of Grade ≥3 cytokine release syndrome (CRS) associated with any T-cell redirecting therapy (e.g., CD3-redirecting therapies or CAR-T cell therapy).
• Presence of conditions affecting intravenous infusion or blood collection, dysphagia, chronic diarrhea, intestinal obstruction, or other active gastrointestinal dysfunction that may interfere with drug administration or absorption.
• Known central nervous system (CNS) involvement of multiple myeloma (MM), or clinical signs/symptoms suggestive of leptomeningeal involvement. If either is suspected, both brain MRI and lumbar puncture cytology must be negative.
• Major surgery, significant traumatic injury, or planned major surgery during the study treatment period within 4 weeks prior to randomization, or presence of non-healed wounds or fractures (major surgery defined as Grade ≥3 according to the 2022 national surgical classification catalogue).
• Any severe (≥ CTCAE Grade 3) bleeding or hemorrhagic event within 6 months prior to randomization.
• Arterial or venous thrombotic events within 6 months prior to randomization, including cerebrovascular events (including transient ischemic attack), deep vein thrombosis, pulmonary embolism, or any other serious thromboembolism (implantable venous port- or catheter-related thrombosis and superficial thrombosis are not considered "serious").
• Active hepatitis or decompensated cirrhosis (Child-Pugh Class B or C)
• Significant cardiovascular disease.
• Neurological or psychiatric disorders.
• Pulmonary diseases, including any of the following:

• Current or prior non-infectious pneumonitis requiring corticosteroid treatment (including but not limited to acute respiratory distress syndrome, acute hypersensitivity pneumonitis, drug-related pneumonitis, bronchospasm, acute interstitial pneumonitis, idiopathic pulmonary fibrosis, etc.);
• Known or suspected chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) <60% of predicted.
• Active or uncontrolled infections (≥ CTCAE Grade 2), including bacterial, fungal, or viral infections, such as active pneumonia/pulmonary infection, syphilis, tuberculosis, or Corona Virus Disease 2019 (COVID-19). Subjects with positive Cytomegalovirus (CMV) DNA or Epstein-Barr virus (EBV) plasma DNA during screening are not eligible.
• Current or prior autoimmune diseases requiring systemic treatment. Subjects with hypothyroidism on stable replacement therapy, well-controlled type 1 diabetes, or skin diseases not requiring systemic therapy (e.g., vitiligo, psoriasis) are eligible.
• History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency disorders.
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
• Known history of hypersensitivity to humanized monoclonal antibodies, or known allergy, hypersensitivity, or intolerance to any component of the investigational product.
• Any other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that, in the investigator's opinion, may increase the risk associated with study participation or interfere with interpretation of study results.
• Investigator considers that the subject is likely to have poor compliance with study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 49 centers

• The First Affiliated Hospital of Bengbu Medical University — Bengbu
• The First Affiliated Hospital of Anhui Medical University — Hefei
• Beijing Chao-Yang Hospital,Capital Medical University — Beijing
• Beijing Jishuitan Hospital,Capital Medical University — Beijing
• The First Affiliated Hospital of Chongqing Medical University — Chongqing
• The Southwest Hospital of Amu — Chongqing
• Gansu Provincial Maternal and Child Health Hospital (Gansu Provincial Central Hospital) — Lanzhou
• Lanzhou University Second Hospital — Lanzhou
• … and 41 more centers

Identifiers

NCT: NCT07569757 · TQB2934-III-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗