Dose-Escalation Study, Relapsed or Refractory Multiple Myeloma
Conditions
Brief summary
This trial is a Multiple center, Open-label, dose escalation Phase Ⅰ clinical study. The purpose is to evaluate the safety and tolerability of F182112 when infused intravenously (IV) and determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of F182112 when infused IV.
Detailed description
To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose regimen (RP2DR) of F182112 as monotherapy in patients with relapsed or refractory multiple myeloma (MM).
Interventions
DRUGF182112
Eight dose cohorts: 0.01, 0.1, 0.3, 1, 3, 10, 20 and 30 μg/kg) d1 treat every weeks.
Sponsors
Shandong New Time Pharmaceutical Co., LTD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\) Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures; 2\) Male or female ≥ 18 years; 3\) Patient has a history of multiple myeloma with relapsed and refractory disease, and must: 1. Relapsed after an autologous stem cell transplant (ASCT), or not suitable for ASCT; 2. Must have received at least 2 prior multiple myeloma treatment regimens (not including autologous stem cell transplant) including a proteasome inhibitor, an immunomodulatory agent; 4\) ECOG of 0-2; 5\) Patients must have measurable disease, including at least one of the criteria below: <!-- --> 1. M-protein ≥ 0.5 g/dL by SPEP/immunofixation or 2. ≥ 200 mg/24 hours urine collection by UPEP or 3. Serum free light chain (FLC) levels \> 100 mg/L (milligrams/liter involved light chain) and an abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine M-protein; 6\) Adequate hepatic function as evidenced by meeting all the following requirements: <!-- --> 1. Blood routine: absolute neutrophil count (ANC) ≥ 1.0×109/L, hemoglobin (Hb) ≥70g/L, Platelet ≥ 50×109/L; 2. Liver function: total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 2.5 × ULN, Aspartate aminotransferase (AST) ≤ 2.5 × ULN; 3. Renal function: calculated creatinine clearance (CrCL) ≥ 30 mL/min (Cockroft-Gault Equation). 7\) Recovery to Grade 0-1 from adverse events related to prior anticancer therapy except alopecia, ≤ Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy.
Exclusion criteria
* 1\) Patient has primary light chain amyloidosis or plasma cell leukemia; 2\) Patient has symptomatic central nervous system involvement of multiple myeloma; 3\) Received systemic anti-myeloma therapy within 2 weeks, or received plasma exchange within 4 weeks; 4\) Received any experimental drugs within 4 weeks or 5 half-lives (whichever is shorter); 5\) Patient has received ≥ 40 mg/day dexamethasone equivalent within 7 days before starting F182112. Short term use of corticosteroids at doses equivalent to \> 10 mg/d of prednisone； 6\) Received any monoclonal antibody therapy within 30 days; 7\) Prior treatment with any B cell maturation antigen (BCMA) targeted therapy; 8\) Patient had a prior allogeneic stem cell transplant or had a prior autologous stem cell transplant ≤ 3 months prior to starting F182112; 9\) Live virus vaccine within 30 days prior to study entry; 10\) Major surgery within 4 weeks prior to study entry; 11\) Concurrent malignancy within 3 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer under active surveillance, prostate cancer that has undergone definitive treatment, ductal carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma; 12\) Patients with active mucosa or visceral bleeding; 13\) Severe cardiovascular disease, including CVA, TIA, myocardial infarction, or unstable angina within 6 months of study entry; NYHA class III or IV heart failure within 6 months of study entry; Uncontrolled arrhythmia within 6 months of study entry. Patients with a rate-controlled arrhythmia may be eligible for study entry at the discretion of the Medical Monitor; 14\) Active infection requiring antibiotic, antiviral or antifungul therapy; 15\) Active viral hepatitis; 16\) Has a history of immunodeficiency, include HIV infection; 17\) Treponema pallidum infection; 18\) Received any experimental drugs or anti-tumor drugs within 2 weeks; 19\) Subject has any condition that confounds the ability to interpret data from the study; 20\) Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and 6 months after the last giving F182112; 21\) Any condition that the investigator or primary physician believes may not be appropriate for participating the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D | Approximately 12 months | Preliminary Antitumor Activity of F182112 at the RP2D(s) in Part 2 |
| DLTs | Up to 28 days | Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period |
| Maximum Tolerated Dose (MTD) | Approximately 12 months | Maximum Tolerated Dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Approximately 24 months | Objective remission rate was used to evaluate the efficacy of F182112 injection in patients with MM. |
| Overall survival (OS) | Approximately 24 months | To evaluate the duration from the first dose to death of patients with MM for any reason. |
| Progression-free survival (PFS) | Approximately 24 months | Evaluation of the efficacy of F182112 in patients with MM on progression-free survival. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD) Negative Rate | Approximately 24 months | Minimal Residual Disease (MRD) Negative Rate |
Countries
China
Outcome results
None listed