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出境医 / 临床实验 / A Study of TNB-383B in Subjects With Relapsed or Refractory Multiple Myeloma

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

Study Description
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, administered once every 3 weeks (Q3W), in approximately 85 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

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 133 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 : December 2021
Estimated Study Completion Date : December 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Arm A: Dose Escalation
Up to 15 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 maximum tolerated dose or 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.
Outcome Measures
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.


Eligibility Criteria
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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 (e.g., 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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Ben Buelow, MD, PhD (650) 899-8222 studydirector@teneobio.com

Locations
Layout table for location information
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 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
Layout table for investigator information
Study Chair: Ben Buelow, MD, PhD Teneobio, Inc.
Tracking Information
First Submitted Date  ICMJE April 26, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date December 19, 2020
Actual Study Start Date  ICMJE June 24, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current 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.
Original Secondary Outcome Measures  ICMJE Same as current
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 Subjects 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 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, administered once every 3 weeks (Q3W), in approximately 85 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
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
TNB-383B is a bispecific antibody targeting BCMA on tumor cells and CD3 on T-cells.
Study Arms  ICMJE
  • Experimental: Arm A: Dose Escalation
    Up to 15 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.
    Intervention: Drug: TNB-383B
  • Experimental: Arm B: Dose Expansion
    An expansion cohort will be enrolled after maximum tolerated dose or recommended phase 2 dose is established.
    Intervention: Drug: TNB-383B
Publications * Not Provided

*   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: December 16, 2020) 		133
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2019) 		72
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (e.g., 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
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: Ben Buelow, MD, PhD (650) 899-8222 studydirector@teneobio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03933735
Other Study ID Numbers  ICMJE TNB383B.0001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Teneobio, Inc.
Study Sponsor  ICMJE Teneobio, Inc.
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Study Chair: Ben Buelow, MD, PhD Teneobio, Inc.
PRS Account Teneobio, Inc.
Verification Date December 2020

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

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