Phase 1 Study of F182112 in Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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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
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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).

Official Title
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A First-in-human, Open-label, Multiple Center Phase 1 Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetic, Immunogenicity, and Preliminary Efficacy of F182112 in Patients With Relapsed or Refractory Multiple Myeloma.

Conditions
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Dose-Escalation Study, Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: F182112


Participation Criteria
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Eligibility Criteria
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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: Relapsed after an autologous stem cell transplant (ASCT), or not suitable for ASCT; 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: M-protein ≥ 0.5 g/dL by SPEP/immunofixation or ≥ 200 mg/24 hours urine collection by UPEP or 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: Blood routine: absolute neutrophil count (ANC) ≥ 1.0×109/L, hemoglobin (Hb) ≥70g/L, Platelet ≥ 50×109/L; Liver function: total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 2.5 × ULN, Aspartate aminotransferase (AST) ≤ 2.5 × ULN; 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.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Single Arm<br> | Drug: F182112<br>* Eight dose cohorts: 0.01, 0.1, 0.3, 1, 3, 10, 20 and 30 μg/kg) d1 treat every weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLTs | Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period | Up to 28 days | 
| Maximum Tolerated Dose (MTD) | Maximum Tolerated Dose | Approximately 12 months | 
| RP2D | Preliminary Antitumor Activity of F182112 at the RP2D(s) in Part 2 | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | To evaluate the duration from the first dose to death of patients with MM for any reason. | Approximately 24 months | 
| Progression-free survival (PFS) | Evaluation of the efficacy of F182112 in patients with MM on progression-free survival. | Approximately 24 months | 
| Objective response rate (ORR) | Objective remission rate was used to evaluate the efficacy of F182112 injection in patients with MM. | Approximately 24 months |