Clinical Trials /

A Study of TNB-383B in Subjects With Relapsed or Refractory Multiple Myeloma

NCT03933735

Description:

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific antibody, in subjects with relapsed or refractory MM who have received at least 3 prior lines of therapy. The study consists of 2 portions, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Arm A will evaluate the safety, tolerability, PK and PD profiles of escalating doses of single-agent TNB-383B ranging from 25 micrograms to 40 milligrams per dose, administered once every 3 weeks (Q3W), in approximately 24 subjects. Once the maximum tolerated dose (MTD) or recommended phase 2 dose, (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the MTD/RP2D dose of TNB 383B monotherapy in approximately 48 subjects.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of TNB-383B in Subjects With Relapsed or Refractory Multiple Myeloma
  • Official Title: A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of TNB-383B, a Bispecific Antibody Targeting BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: TNB383B.0001
  • NCT ID: NCT03933735

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
TNB-383BArm A: Dose Escalation

Purpose

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-383B, a BCMA x CD3 T-cell engaging bispecific antibody, in subjects with relapsed or refractory MM who have received at least 3 prior lines of therapy. The study consists of 2 portions, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Arm A will evaluate the safety, tolerability, PK and PD profiles of escalating doses of single-agent TNB-383B ranging from 25 micrograms to 40 milligrams per dose, administered once every 3 weeks (Q3W), in approximately 24 subjects. Once the maximum tolerated dose (MTD) or recommended phase 2 dose, (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the MTD/RP2D dose of TNB 383B monotherapy in approximately 48 subjects.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Dose EscalationExperimental9 cohorts of subjects receiving sequentially ascending doses of TNB-383B are planned until maximum tolerated dose is reached or recommended phase 2 dose is identified.
  • TNB-383B
Arm B: Dose ExpansionExperimentalAn expansion cohort will be enrolled after recommended phase 2 dose is established.
  • TNB-383B

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects with Relapsed/Refractory Multiple Myeloma.

          -  Subject has received three or more prior lines of therapy with exposure to a
             proteasome inhibitor (PI), an immunomodulatory imide (IMiD) and an anti-CD38
             monoclonal antibody (ie, daratumumab).

          -  Subject has Measurable Disease, defined as at least 1 of the following:

               -  Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L)

               -  Urine M-protein ≥ 200 mg / 24h

               -  Serum free light chain (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/L)
                  and an abnormal serum FLC ratio (< 0.26 or > 1.65).

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          -  Prior bone marrow transplant is acceptable if subject is > 12 weeks (autologous) or >
             1 year (allogeneic) status-post transplantation

          -  Subject must have adequate bone marrow function, defined as:

               -  absolute neutrophil count (ANC) ≥ 1000/mm3;

               -  platelets ≥ 50,000/mm3;

               -  hemoglobin ≥ 8.0 g/dL.

          -  Subject must have an eGFR ≥ 30 mL/min as estimated by the MDRD formula.

          -  Subject must have total bilirubin ≤ 1.5 × upper limit of normal (ULN; except if the
             subject has a known diagnosis of Gilbert's syndrome, in which case bilirubin must be <
             3 x ULN).

          -  Serum calcium (corrected for albumin) at or below the ULN range.

        Exclusion Criteria:

          -  Subject has ever received BCMA-targeted therapy. Subjects who have received targeted
             therapy against non-BCMA targets will not be excluded

          -  Subject has a history of central nervous system involvement by their myeloma.

          -  Subject has a history of ≥ Grade 3 peripheral neuropathy.

          -  Subject has a history of plasma cell leukemia, POEMS syndrome, or amyloidosis.

          -  Subject has received any therapy to treat cancer or undergone a major surgical
             procedure within 21 days, or within 5 half-lives of an anticancer drug, prior to the
             first dose of study treatment, whichever is shorter.

          -  Subject has a history of major cardiac abnormalities.

          -  Subject has a known active infection requiring parenteral anti-infective treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with Dose-limiting toxicities (DLT)
Time Frame:21 days
Safety Issue:
Description:The incidence, timing, seriousness, and relationship to study treatments of adverse events will be evaluated. An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.

Secondary Outcome Measures

Measure:Incidence of Anti-drug Antibody (ADA)
Time Frame:48 months
Safety Issue:
Description:The number of participants with anti-TNB-383B antibodies
Measure:Titers of Anti-drug Antibody (ADA)
Time Frame:48 months
Safety Issue:
Description:The titers of anti-TNB-383B antibodies
Measure:Anti-Myeloma Activity by Objective Response Rate (ORR)
Time Frame:48 months
Safety Issue:
Description:The objective response rate, defined as the proportion of subjects with a confirmed partial (PR) or complete (CR) response to treatment as determined using International Myeloma Working Group (IMWG) uniform response criteria
Measure:Anti-Myeloma Activity by Duration of Objective Response (DOR)
Time Frame:48 months
Safety Issue:
Description:Duration of objective response is measured as the time from the initial objective response to disease progression or death, whichever occurs first.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Teneobio, Inc.

Last Updated

November 19, 2019