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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Dose-Escalation Study, Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: F182112

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).

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Linyi, Shandong, China, 276006
      • Recruiting
      • Shaohong Yin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal Residual Disease (MRD) Negative Rate	Minimal Residual Disease (MRD) Negative Rate	Approximately 24 months

Collaborators and Investigators

• Sponsor: Shandong New Time Pharmaceutical Co., LTD

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 30, 2021
• Primary Completion (ANTICIPATED): July 30, 2023
• Study Completion (ANTICIPATED): December 30, 2023

Study Registration Dates

• First Submitted: July 21, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (ACTUAL): July 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: NTP-F182112-001

Drug and device information, study documents

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