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

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ClinicalTrials.gov Identifier: NCT03933735
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : November 21, 2019
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Teneobio, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: TNB-383B Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 24, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm A: Dose Escalation
9 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.
Drug: TNB-383B
TNB-383B is a bispecific antibody targeting BCMA on tumor cells and CD3 on T-cells.

Experimental: Arm B: Dose Expansion
An expansion cohort will be enrolled after recommended phase 2 dose is established.
Drug: TNB-383B
TNB-383B is a bispecific antibody targeting BCMA on tumor cells and CD3 on T-cells.




Primary Outcome Measures :
  1. Number of subjects with Dose-limiting toxicities (DLT) [ Time Frame: 21 days ]
  2. Number of subjects with adverse events (AEs) and/or serious adverse events (SAEs) [ Time Frame: From screening until 90 Days after end of treatment ]
    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.

  3. Maximum Observed Plasma Concentration of TNB-383B (Cmax) [ Time Frame: 12 weeks ]
    Cmax of TNB-383B will be calculated

  4. Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) [ Time Frame: 12 weeks ]
    AUClast of TNB-383B will be calculated.

  5. Apparent terminal half-life (t1/2) of TNB-383B. [ Time Frame: 12 weeks ]
    t1/2 of TNB-383B will be calculated


Secondary Outcome Measures :
  1. Incidence of Anti-drug Antibody (ADA) [ Time Frame: 48 months ]
    The number of participants with anti-TNB-383B antibodies

  2. Titers of Anti-drug Antibody (ADA) [ Time Frame: 48 months ]
    The titers of anti-TNB-383B antibodies

  3. Anti-Myeloma Activity by Objective Response Rate (ORR) [ Time Frame: 48 months ]
    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

  4. Anti-Myeloma Activity by Duration of Objective Response (DOR) [ Time Frame: 48 months ]
    Duration of objective response is measured as the time from the initial objective response to disease progression or death, whichever occurs first.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03933735


Contacts
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Contact: Ben Buelow, MD, PhD (650) 899-8222 studydirector@teneobio.com

Locations
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United States, California
UCSF Recruiting
San Francisco, California, United States, 94143
United States, Minnesota
Mayo Clinic-Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Carolinas Healthcare Not yet recruiting
Charlotte, North Carolina, United States, 28204
Wake Forest Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Teneobio, Inc.
AbbVie
Investigators
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Study Chair: Ben Buelow, MD, PhD Teneobio, Inc.

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Responsible Party: Teneobio, Inc.
ClinicalTrials.gov Identifier: NCT03933735     History of Changes
Other Study ID Numbers: TNB383B.0001
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: November 21, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs