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Trial record 1 of 1 for:    NCT03933735
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A Study of TNB-383B in Participants 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 : August 23, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
TeneoOne Inc.

Tracking Information
First Submitted Date  ICMJE April 26, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date August 23, 2022
Actual Study Start Date  ICMJE June 24, 2019
Estimated Primary Completion Date August 24, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 12, 2022)
  • 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.
  • 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.
  • Maximum Observed Plasma Concentration of TNB-383B (Cmax) [ Time Frame: Week 12 ]
    Cmax of TNB-383B.
  • Time to Cmax of TNB-383B (Tmax) [ Time Frame: Week 12 ]
    Time to maximum plasma concentration (Tmax) of TNB-383B.
  • 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.
  • Clearance (CL) of TNB-383B [ Time Frame: Week 12 ]
    Clearance is defined the volume of plasma cleared of the drug per unit time.
  • Terminal Phase Elimination Rate Constant (Beta) of TNB-383B [ Time Frame: Week 12 ]
    Apparent terminal phase elimination rate constant of TNB-383B.
  • Terminal Half-Life (t1/2) of TNB-383B [ Time Frame: Week 12 ]
    Terminal half-life (t1/2) of TNB-383B.
  • Number of Participants with of Anti-drug Antibody (ADA) [ Time Frame: Up to Month 48 ]
    The number of participants with anti-TNB-383B antibodies.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Number of subjects with Dose-limiting toxicities (DLT) [ Time Frame: 21 days ]
  • 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.
  • Maximum Observed Plasma Concentration of TNB-383B (Cmax) [ Time Frame: 12 weeks ]
    Cmax of TNB-383B will be calculated
  • 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.
  • Apparent terminal half-life (t1/2) of TNB-383B. [ Time Frame: 12 weeks ]
    t1/2 of TNB-383B will be calculated
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2022)
  • 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]).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Incidence of Anti-drug Antibody (ADA) [ Time Frame: 48 months ]
    The number of participants with anti-TNB-383B antibodies
  • Titers of Anti-drug Antibody (ADA) [ Time Frame: 48 months ]
    The titers of anti-TNB-383B antibodies
  • 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
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of TNB-383B in Participants With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Drug: TNB-383B
Intravenous (IV) Injection
Study Arms  ICMJE
  • 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.
    Intervention: Drug: TNB-383B
  • Experimental: Arm B: Dose Expansion Dose A
    An expansion cohort will be enrolled at the recommended phase 2 Dose A.
    Intervention: Drug: TNB-383B
  • Experimental: Arm B: Dose Expansion Dose B
    An expansion cohort will be enrolled at the recommended phase 2 Dose B.
    Intervention: Drug: TNB-383B
  • Experimental: Arm E: Monotherapy Once Every 4 Weeks (Q4W)
    An expansion cohort will be enrolled at the recommended phase 2 Dose A.
    Intervention: Drug: TNB-383B
  • Experimental: Arm F: Monotherapy Dose C
    An expansion cohort will be enrolled at the recommended phase 2 Dose C.
    Intervention: Drug: TNB-383B
Publications * D'Souza A, Shah N, Rodriguez C, Voorhees PM, Weisel K, Bueno OF, Pothacamury RK, Freise KJ, Yue S, Ross JA, Polepally AR, Talati C, Lee S, Jin Z, Buelow B, Vij R, Kumar S. A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. J Clin Oncol. 2022 Aug 27:JCO2201504. doi: 10.1200/JCO.22.01504. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 4, 2022)
214
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
72
Estimated Study Completion Date  ICMJE August 24, 2025
Estimated Primary Completion Date August 24, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03933735
Other Study ID Numbers  ICMJE TNB383B.0001
2020-000199-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party TeneoOne Inc.
Original Responsible Party Amgen
Current Study Sponsor  ICMJE TeneoOne Inc.
Original Study Sponsor  ICMJE Amgen
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Study Director: TeneoOne Inc TeneoOne Inc.
PRS Account TeneoOne Inc.
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP