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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03933735
• Other study ID #: TNB383B.0001
• Secondary ID: 2020-000199-40
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 24, 2019
• Est. completion date: May 12, 2026

Study information

• Verified date: November 2023
• Source: TeneoOne Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 220
• Est. completion date: May 12, 2026
• Est. primary completion date: May 12, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• TNB-383B
Intravenous (IV) Injection

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 239638	Dresden
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 239636	Hamburg
Germany	Universitaetsklinikum Koeln /ID# 239676	Köln	Nordrhein-Westfalen
Germany	Universitaetsklinikum Muenster /ID# 239637	Muenster	Nordrhein-Westfalen
United States	University of North Carolina /ID# 238685	Chapel Hill	North Carolina
United States	Levine Cancer Ins, Carolina Me /ID# 238786	Charlotte	North Carolina
United States	Medical College of Wisconsin /ID# 238684	Milwaukee	Wisconsin
United States	Tulane University /ID# 242322	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831	New York	New York
United States	Mt Sinai /ID# 242317	New York	New York
United States	Mayo Clinic - Rochester /ID# 238683	Rochester	Minnesota
United States	Washington University-School of Medicine /ID# 238681	Saint Louis	Missouri
United States	University of California San Francisco Medical Center /ID# 238680	San Francisco	California
United States	Wake Forest Univ HS /ID# 238787	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
TeneoOne Inc.	AbbVie

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Maximum Observed Plasma Concentration of TNB-383B (Cmax)	Cmax of TNB-383B.	Week 12
Primary	Time to Cmax of TNB-383B (Tmax)	Time to maximum plasma concentration (Tmax) of TNB-383B.	Week 12
Primary	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
Primary	Clearance (CL) of TNB-383B	Clearance is defined the volume of plasma cleared of the drug per unit time.	Week 12
Primary	Terminal Phase Elimination Rate Constant (Beta) of TNB-383B	Apparent terminal phase elimination rate constant of TNB-383B.	Week 12
Primary	Terminal Half-Life (t1/2) of TNB-383B	Terminal half-life (t1/2) of TNB-383B.	Week 12
Primary	Number of Participants with of Anti-drug Antibody (ADA)	The number of participants with anti-TNB-383B antibodies.	Up to Month 48
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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