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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Giant Cell Tumor of Bone
• Intervention / Treatment: Drug: Narlumosbart; Drug: Denosumab

• Study Type: Interventional
• Enrollment (Anticipated): 146
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group Officer; Phone Number: +86-0311-69085587; Email: ctr-contact@mail.ecspc.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100035
      • Beijing Ji Shui Tan Hospital
      • Contact: Xiaohui Niu, B.M.; Phone Number: +86-010-58516506; Email: niuxiaohui@263.net

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Fully informed and signed informed consent;
2. Male or female adults aged ≥ 18 years or skeletally mature adolescents must weigh at least 45 kg and ≥ 12 years of age;
3. Pathologically confirmed giant cell tumor of bone that is surgically unresectable or for which the planned surgery is associated with functional compromise or morbidity;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

Exclusion Criteria:

1. 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;
2. Known or suspected diagnosis of other giant cell-rich tumors, brown cell tumor of bone, or Paget's disease;
3. Known diagnosis of malignancy within the past 5 years, except for definitively treated superficial basal cell carcinoma or cervical carcinoma in situ;
4. Bone metabolic disease including hypo-/hyperparathyroidism, hypo-/hyperthyroidism (except for no need treatment subclinical hypothyroidism), hypopituitarism, hyperprolactinemia, Cushing's syndrome, acromegaly, etc.;
5. Active infections requiring systematic treatment within 7 days prior to randomization;
6. Known human immunodeficiency virus (HIV), syphilis infections or viral hepatitis;
7. Current receiving other anti-tumor therapy (such as radiation, chemotherapy, or embolization, etc.);
8. Concurrent bisphosphonate treatment;
9. 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;
10. Known allergic/hypersensitive reaction to JMT103, positive control drug, calcium and vitamin D;
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Narlumosbart; 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; 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.; Other Names: JMT103
Active Comparator: Denosumab; 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; 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.; Other Names: XGEVA

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease Control Rate (DCR)	Up to approximately 4 years
Percentage of Patients With Giant Cell Objective Tumor Response	Throughout the study period, 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)

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.
• Investigators: Principal Investigator: Xiaohui Niu, B.M., Beijing Ji Shui Tan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): June 1, 2028
• Study Completion (Anticipated): September 1, 2028

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 3, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 16, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Giant Cell Tumor of Bone
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Bone Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Bone Neoplasms; Giant Cell Tumors; Giant Cell Tumor of Bone; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: JMT103-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No