Clinical trial NCT04630522: Efficacy and Safety of JMT103 in Patients With Bone Metastases From Solid Tumors
Official title: A Randomized, Open-Label, Dose-finding, Multi-centre, Phase Ib Study toEvaluate the Efficacy and Safety of JMT103 in Patients With Bone Metastases From Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bone Metastases From Solid Tumors
Lead sponsor: Shanghai JMT-Bio Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, dose-finding, multi-centre, phase Ⅰb study to evaluate the efficacy and safety of JMT103 in patients with bone metastases from solid tumors.

Detailed description: The objective of this trial is to evaluate the efficacy and safety of JMT103 in patients with bone metastases from solid tumors.

Eligible patients will be randomly assigned to receive JMT103 120mg subcutaneously (SC) every 4 weeks (Q4W), 120mg subcutaneously (SC) every 8 weeks (Q8W) and 180mg subcutaneously (SC) every 8 weeks (Q8W) in a 1:1:1 ratio. Patients will receive the treatment until the completion of 48 weeks of treatment, intolerable toxicity, loss to follow-up, withdrawal (patient's decision or investigator's decision), whichever comes first.

Eligibility criteria: Inclusion Criteria:

1. Fully informed and signed informed consent.
2. Male or female, 18 years and older.
3. Histologically/cytologically confirmed malignant solid tumors.
4. Radiographic evidence of at least one bone metastasis.
5. Eligible fertile patients (male and female) must agree to use an effective method of contraception with their partners from the signing of informed consent until at least 6 months after the last treatment.
6. Adequate organ functions.
7. Albumin-corrected serum calcium ≥ 1 x lower limit of normal (LLN) at screening (calcium supplement is not allowed within 8 hours prior to screening).
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
9. Life expectancy ≥ 6 months

Exclusion Criteria:

1. Previous or present osteomyelitis or osteonecrosis of the jaw; unhealed dental or oral surgery wounds; acute disease of the tooth or jaw requiring oral surgery; and invasive dental surgery planned to be received during the study;
2. Radiotherapy or orthopaedic surgery is planned for patients during the study;
3. Known symptomatic brain metastases.
4. Abnormal bone metabolism (such as Paget's disease, Cushing's syndrome, hyperprolactinemia), rheumatoid arthritis, parathyroid disease
5. Clinically significant disease (such as uncontrolled diabetes, congestive heart failure, hypertension\>150/90 mmHg).
6. Known hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or other active viral infection.
7. Systemic therapy of active bacterial infection or fungal infection within 7 days prior to randomization.
8. Pregnant or lactating women.
9. Prior use of antibody against nuclear factor kappa-B (NFκB) ligand (RANKL).
10. Participated in other clinical studies and received other experimental drugs within 4 weeks prior to randomization.
11. Prior use of bisphosphonate within 4 weeks prior to randomization.
12. Prior use of one of following osteoporosis medications within 6 months prior to randomization (Parathyroid hormone (PTH) analogue, calcitonin, osteoprotegerin, mithramycin, and strontium).
13. Adverse reactions from the previous anti-tumor treatment have not yet recovered to ≤ level 1 based on CTCAE 5.0 (except for the toxicity without safety risk judged by the investigator, such as hair loss)
14. Known hypersensitivity to any of the products to be administered during the study (such as JMT103)
15. Not suitable for this study as determined by the investigator due to other reasons.

Primary outcomes:
measure: Percentage change of urinary N-terminal telopeptide of type 1 collagen/creatine (U-NTX/Cr) from baseline to week 13
timeFrame: From enrollment to week 13.
Secondary outcomes:
measure: Incidence and type of adverse events (AEs)
timeFrame: From enrollment to 90 days after the last dose
measure: Incidence of Skeletal-related event（SRE）
timeFrame: From enrollment to 90 days after the last dose
measure: Change in Pain Score (Brief Pain Inventory-Short Form，BPI-SF)
timeFrame: From enrollment to 90 days after the last dose
measure: Trough plasma concentration （Ctrough）
timeFrame: From enrollment to 90 days after the last dose
measure: Percentage change in serum C-terminus peptide (of Type 1 Collagen) from baseline
timeFrame: From enrollment to 90 days after the last dose
measure: Percentage change in serum bone-specific alkaline phosphatase (bALP) from baseline
timeFrame: From enrollment to 90 days after the last dose
measure: Number of patients with anti-JMT103 antibodies
timeFrame: From enrollment to 90 days after the last dose
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital
name: Jin Li, MD
role: PRINCIPAL_INVESTIGATOR
References: