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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Intravenous (IV) Injection
University of California San Francisco (UCSF) - Parnassus Heights /ID# 238680
San Francisco, California, United States
Tulane University School of Medicine /ID# 242322
New Orleans, Louisiana, United States
Mayo Clinic - Rochester /ID# 238683
Rochester, Minnesota, United States
Washington University-School of Medicine /ID# 238681
St Louis, Missouri, United States
Mt Sinai /ID# 242317
New York, New York, United States
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831
New York, New York, United States
University of North Carolina /ID# 238685
Chapel Hill, North Carolina, United States
Atrium Health Levine Cancer Institute /ID# 238786
Charlotte, North Carolina, United States
Atrium Health Wake Forest Baptist Medical Center /ID# 238787
Winston-Salem, North Carolina, United States
Wisconsin Medical Center /ID# 238684
Milwaukee, Wisconsin, United States
...and 4 more locations
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.
Time frame: 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.
Time frame: Up to 3 Years
Maximum Observed Plasma Concentration of TNB-383B (Cmax)
Cmax of TNB-383B.
Time frame: Week 12
Time to Cmax of TNB-383B (Tmax)
Time to maximum plasma concentration (Tmax) of TNB-383B.
Time frame: 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.
Time frame: Week 12
Clearance (CL) of TNB-383B
Clearance is defined the volume of plasma cleared of the drug per unit time.
Time frame: Week 12
Terminal Phase Elimination Rate Constant (Beta) of TNB-383B
Apparent terminal phase elimination rate constant of TNB-383B.
Time frame: Week 12
Terminal Half-Life (t1/2) of TNB-383B
Terminal half-life (t1/2) of TNB-383B.
Time frame: Week 12
Number of Participants with of Anti-drug Antibody (ADA)
The number of participants with anti-TNB-383B antibodies.
Time frame: Up to Month 48
Objective Response Rate (ORR)
ORR is defined as confirmed Stringent complete response (sCR) + Complete response (CR) + very good partial response + partial response \[PR\]).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 48 Months
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