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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: TNB-383B

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 239638
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 239636
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Universitaetsklinikum Koeln /ID# 239676
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • Universitaetsklinikum Muenster /ID# 239637
• United States
  • California
    • San Francisco, California, United States, 94143-0324
      • University of California San Francisco Medical Center /ID# 238680
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2699
      • Tulane University /ID# 242322
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Rochester /ID# 238683
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University-School of Medicine /ID# 238681
  • New York
    • New York, New York, United States, 10029-6542
      • Mt Sinai /ID# 242317
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina /ID# 238685
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Ins, Carolina Me /ID# 238786
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Univ HS /ID# 238787
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Medical College of Wisconsin /ID# 238684

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose-limiting toxicities (DLT)	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.	Day 21
Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs)	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.	Up to 3 Years
Maximum Observed Plasma Concentration of TNB-383B (Cmax)	Cmax of TNB-383B.	Week 12
Time to Cmax of TNB-383B (Tmax)	Time to maximum plasma concentration (Tmax) of TNB-383B.	Week 12
Area Under the Concentration Versus Time Curve from Time Zero to the Last Measurable Concentration (AUClast)	Area under the concentration versus time curve from time zero to the last measurable concentration of TNB-383B.	Week 12
Clearance (CL) of TNB-383B	Clearance is defined the volume of plasma cleared of the drug per unit time.	Week 12
Terminal Phase Elimination Rate Constant (Beta) of TNB-383B	Apparent terminal phase elimination rate constant of TNB-383B.	Week 12
Terminal Half-Life (t1/2) of TNB-383B	Terminal half-life (t1/2) of TNB-383B.	Week 12
Number of Participants with of Anti-drug Antibody (ADA)	The number of participants with anti-TNB-383B antibodies.	Up to Month 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as confirmed Stringent complete response (sCR) + Complete response (CR) + very good partial response + partial response [PR]).	Up to Month 48
Percentage of Participants with Overall Survival (OS)	OS is defined as time from the first dose of TNB-383B to the date of death, from any cause.	Up to 48 Months
Percentage of Participants with Progression-Free Survival (PFS)	Progression-free survival time is defined as the time from the first dose of TNB-383B to progression or death, whichever occurs first.	Up to 48 Months
Time-to-Progression (TTP)	TTP is defined as the time from the first dose of TNB-383B to the date of the first documented disease progression.	Up to 48 Months
Time-to-Response (TTR)	TTR is defined as the time from the first dose of TNB-383B to the date of the first assessment having documented the response.	Up to 48 Months
Duration of Objective Response (DOR)	DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.	Up to 48 Months

Collaborators and Investigators

• Sponsor: TeneoOne Inc.
• Collaborators: AbbVie
• Investigators: Study Director: TeneoOne Inc, TeneoOne Inc.

Publications and helpful links

General 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 x CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. J Clin Oncol. 2022 Nov 1;40(31):3576-3586. doi: 10.1200/JCO.22.01504. Epub 2022 Aug 27.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2019
• Primary Completion (Estimated): May 12, 2026
• Study Completion (Estimated): May 12, 2026

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; TNB-383B
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: TNB383B.0001; 2020-000199-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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