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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03933735
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : August 23, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
TeneoOne 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 participants with relapsed or refractory MM who have received at least 3 prior lines of therapy. The study consists of 4 portions, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B), Monotherapy once every 4 weeks (Q4W) dosing (Arm E), Monotherapy once every 3 weeks (Q3W) dosing (Arm F). Arm A will evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of escalating doses of single-agent TNB-383B, administered Q3W, in approximately 73 participants. 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, PK and PD profiles of the MTD/RP2D 2 dose expansion arms of 48 participants each. Dose A will be evaluated as a monotherapy Q4W, in Arm E to further characterize the safety, tolerability, PK and PD profiles of the MTD/RP2D 2 dose expansion arms of 20 participants. Dose C will be evaluated as a monotherapy, in Arm F to further characterize the safety, tolerability, PK and PD profiles of the MTD/RP2D 2 dose expansion arms of 25 participants.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: TNB-383B Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 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 : August 24, 2025
Estimated Study Completion Date : August 24, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm A: Dose Escalation
Up to 15 cohorts of participants 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
Intravenous (IV) Injection

Experimental: Arm B: Dose Expansion Dose A
An expansion cohort will be enrolled at the recommended phase 2 Dose A.
Drug: TNB-383B
Intravenous (IV) Injection

Experimental: Arm B: Dose Expansion Dose B
An expansion cohort will be enrolled at the recommended phase 2 Dose B.
Drug: TNB-383B
Intravenous (IV) Injection

Experimental: Arm E: Monotherapy Once Every 4 Weeks (Q4W)
An expansion cohort will be enrolled at the recommended phase 2 Dose A.
Drug: TNB-383B
Intravenous (IV) Injection

Experimental: Arm F: Monotherapy Dose C
An expansion cohort will be enrolled at the recommended phase 2 Dose C.
Drug: TNB-383B
Intravenous (IV) Injection




Primary Outcome Measures :
  1. Number of Participants with Dose-limiting toxicities (DLT) [ Time Frame: Day 21 ]
    A DLT is defined as a Treatment-emergent adverse event that is not unequivocally due to the participant's underlying malignancy or other extraneous cause.

  2. Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) [ Time Frame: Up to 3 Years ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.

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

  4. Time to Cmax of TNB-383B (Tmax) [ Time Frame: Week 12 ]
    Time to maximum plasma concentration (Tmax) of TNB-383B.

  5. Area Under the Concentration Versus Time Curve from Time Zero to the Last Measurable Concentration (AUClast) [ Time Frame: Week 12 ]
    Area under the concentration versus time curve from time zero to the last measurable concentration of TNB-383B.

  6. Clearance (CL) of TNB-383B [ Time Frame: Week 12 ]
    Clearance is defined the volume of plasma cleared of the drug per unit time.

  7. Terminal Phase Elimination Rate Constant (Beta) of TNB-383B [ Time Frame: Week 12 ]
    Apparent terminal phase elimination rate constant of TNB-383B.

  8. Terminal Half-Life (t1/2) of TNB-383B [ Time Frame: Week 12 ]
    Terminal half-life (t1/2) of TNB-383B.

  9. Number of Participants with of Anti-drug Antibody (ADA) [ Time Frame: Up to Month 48 ]
    The number of participants with anti-TNB-383B antibodies.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to Month 48 ]
    ORR is defined as confirmed Stringent complete response (sCR) + Complete response (CR) + very good partial response + partial response [PR]).

  2. Percentage of Participants with Overall Survival (OS) [ Time Frame: Up to 48 Months ]
    OS is defined as time from the first dose of TNB-383B to the date of death, from any cause.

  3. Percentage of Participants with Progression-Free Survival (PFS) [ Time Frame: Up to 48 Months ]
    Progression-free survival time is defined as the time from the first dose of TNB-383B to progression or death, whichever occurs first.

  4. Time-to-Progression (TTP) [ Time Frame: Up to 48 Months ]
    TTP is defined as the time from the first dose of TNB-383B to the date of the first documented disease progression.

  5. Time-to-Response (TTR) [ Time Frame: Up to 48 Months ]
    TTR is defined as the time from the first dose of TNB-383B to the date of the first assessment having documented the response.

  6. Duration of Objective Response (DOR) [ Time Frame: Up to 48 Months ]
    DOR is defined 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:

  • 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.
  • Must have adequate bone marrow function as defined in the protocol.
  • Must have an estimated glomerular filtration rate >= 30 mL/min as estimated by the Modification of Diet in Renal Disease formula.
  • 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.
  • 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).
  • Has confirmed evidence of relapse/progression from the immediately prior MM therapy, or participant is relapsed/refractory to the immediately prior MM therapy.
  • Consents to a fresh pretreatment bone marrow tumor biopsy or has adequate archival bone marrow tumor tissue that was collected within 6 months prior to screening and without intervening treatment.

Exclusion Criteria:

  • Has been diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of basal cell or squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate carcinoma after curative therapy, or complete resection/curative therapy of an advanced malignancy.
  • History of central nervous system involvement by their myeloma.
  • History of Grade >= 3 peripheral neuropathy.
  • History of plasma cell leukemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome, or amyloidosis.
  • Has received another investigational drug within 21 days of enrollment.
  • Has ever received BCMA-targeted therapy.
  • Has received a autologous stem cell transplant within 12 weeks or an allogeneic stem cell transplant within 1 year of the first dose of study drug treatment.
  • Has any medical or psychiatric condition which in the opinion of the investigator or study Medical Monitor places the participant at an unacceptably high risk for toxicities, could interfere with successful or safe delivery of therapy, or could interfere with evaluation of the investigational product or interpretation of participant safety or study results.
  • 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.
  • Has known active infection Grade >= 2 requiring anti-infective treatment.
  • Has a history of major cardiac abnormalities.
  • Has unresolved adverse events as defined in the protocol.

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: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com

Locations
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United States, California
University of California San Francisco Medical Center /ID# 238680 Recruiting
San Francisco, California, United States, 94143-0324
United States, Louisiana
Tulane University /ID# 242322 Recruiting
New Orleans, Louisiana, United States, 70112-2699
United States, Minnesota
Mayo Clinic - Rochester /ID# 238683 Recruiting
Rochester, Minnesota, United States, 55905-0001
United States, Missouri
Washington University-School of Medicine /ID# 238681 Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Mt Sinai /ID# 242317 Not yet recruiting
New York, New York, United States, 10029
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831 Recruiting
New York, New York, United States, 10065-6007
United States, North Carolina
University of North Carolina /ID# 238685 Recruiting
Chapel Hill, North Carolina, United States, 27514
Levine Cancer Ins, Carolina Me /ID# 238786 Recruiting
Charlotte, North Carolina, United States, 28204
Wake Forest Univ HS /ID# 238787 Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Texas
Houston Methodist Hospital /ID# 242329 Not yet recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin /ID# 238684 Recruiting
Milwaukee, Wisconsin, United States, 53226-3522
Germany
Universitaetsklinikum Koeln /ID# 239676 Not yet recruiting
Köln, Nordrhein-Westfalen, Germany, 50937
Universitaetsklinikum Muenster /ID# 239637 Completed
Muenster, Nordrhein-Westfalen, Germany, 48149
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 239638 Recruiting
Dresden, Germany, 01307
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 239636 Recruiting
Hamburg, Germany, 20246
Sponsors and Collaborators
TeneoOne Inc.
AbbVie
Investigators
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Study Director: TeneoOne Inc TeneoOne Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: TeneoOne Inc.
ClinicalTrials.gov Identifier: NCT03933735    
Other Study ID Numbers: TNB383B.0001
2020-000199-40 ( EudraCT Number )
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: August 23, 2022
Last Verified: August 2022
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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by TeneoOne Inc.:
Multiple Myeloma
TNB-383B
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