A Study to Evaluate the Efficacy and Safety of Narlumosbart (JMT103) in Patients With Giant Cell Tumor of Bone

Study Overview
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Brief Summary
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This is a phase Ⅲ, multi-center, randomized, double-blind, active-controlled study to evaluate the efficacy and safety of narlumosbart (JMT103) in patients with unresectable or surgically difficult giant cell tumor of bone (GCTB). This clinical trial study hypothesizes narlumosbart administration groups are not inferior to active control administration groups.

Official Title
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A Multi-center, Randomized, Double-blind, Active-controlled, Phase Ⅲ Study to Evaluate Efficacy and Safety of Narlumosbart (JMT103) in Patients With Giant Cell Tumor of Bone

Conditions
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Giant Cell Tumor of Bone

Intervention / Treatment
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* Drug: Narlumosbart
* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully informed and signed informed consent; Male or female adults aged ≥ 18 years or skeletally mature adolescents must weigh at least 45 kg and ≥ 12 years of age; Pathologically confirmed giant cell tumor of bone that is surgically unresectable or for which the planned surgery is associated with functional compromise or morbidity; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Exclusion Criteria: Previous or ongoing osteomyelitis or osteonecrosis of the jaw, non-healed dental/oral surgery, active dental or jaw condition requiring oral surgery, planned invasive dental procedure during the study; Known or suspected diagnosis of other giant cell-rich tumors, brown cell tumor of bone, or Paget's disease; Known diagnosis of malignancy within the past 5 years, except for definitively treated superficial basal cell carcinoma or cervical carcinoma in situ; Bone metabolic disease including hypo-/hyperparathyroidism, hypo-/hyperthyroidism (except for no need treatment subclinical hypothyroidism), hypopituitarism, hyperprolactinemia, Cushing's syndrome, acromegaly, etc.; Active infections requiring systematic treatment within 7 days prior to randomization; Known human immunodeficiency virus (HIV), syphilis infections or viral hepatitis; Current receiving other anti-tumor therapy (such as radiation, chemotherapy, or embolization, etc.); Concurrent bisphosphonate treatment; Use of anti-receptor activator of nuclear factor-κB ligand (RANKL) antibody within six months prior to screening, or no response to previous RANKL antibody treatment; Known allergic/hypersensitive reaction to JMT103, positive control drug, calcium and vitamin D; Pregnant or lactating females; For those of child bearing potential, refusal to use effective contraception methods from signing informed consent to 6 months after last administration.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Narlumosbart<br>Patients will receive narlumosbart 120 mg subcutaneously (SC) once every 4 weeks (Q4W) with a loading dose of 120 mg SC on day 8 and day 15 of the first cycle until one of the following occurred: complete tumor resection, disease progression, intolerable toxicity, decision by the patient to discontinue, or decision by the investigator that the patient could no longer benefit from the treatment. | Drug: Narlumosbart<br>* Administered by subcutaneous injection. Dietary Supplement: Calcium/Vitamin D. All patients should be adequately supplemented with calcium and vitamin D (at least 500 mg of calcium and 400 IU of vitamin D), except in the case of pre-existing hypercalcemia.<br>* Other names: JMT103;|
| Active Comparator: Denosumab<br>Patients will receive denosumab 120 mg subcutaneously (SC) once every 4 weeks (Q4W) with a loading dose of 120 mg SC on day 8 and day 15 of the first cycle until one of the following occurred: complete tumor resection, disease progression without clinical benefit, decision by the patient to discontinue, or decision by the investigator that the patient could no longer benefit from the treatment. | Drug: Denosumab<br>* Administered by subcutaneous injection. Dietary Supplement: Calcium/Vitamin D. All patients should be adequately supplemented with calcium and vitamin D (at least 500 mg of calcium and 400 IU of vitamin D), except in the case of pre-existing hypercalcemia.<br>* Other names: XGEVA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Giant Cell Objective Tumor Response |  | From enrollment until 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Giant Cell Objective Tumor Response |  | Throughout the study period, up to approximately 4 years | 
| Disease Control Rate (DCR) |  | Up to approximately 4 years | 
| Time to Response (TTR) |  | Up to approximately 4 years | 
| Duration of Response (DOR) |  | Up to approximately 4 years | 
| Time to Progression (TTP) |  | Up to approximately 4 years | 
| Percentage of Patients Downstaging the Planned Surgical Procedure |  | From enrollment until surgery, up to approximately 4 years | 
| Time to First Tumor Surgery |  | From enrollment until the first tumor surgery, up to approximately 4 years | 
| Changes in Brief Pain Inventory Short Form (BPI-SF) score |  | From enrollment until the last dose, up to approximately 4 years | 
| Types and Proportion of Key Adverse Reactions |  | From the first dose of study drug until 90 days after the last dose, up to approximately 4 years | 
| Serum JMT103 Concentrations |  | Days 8 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, and 90 days after the last dose (each cycle is 28 days) | 
| Number of Patients with Anti-JMT103 Antibodies |  | Day 1 of Cycle 1, 2, 4, 6, and 90 days after the last dose (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Giant Cell Tumor of Bone