Clinical trial NCT03933735: A Study of TNB-383B in Participants With Relapsed or Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
TNB-383B
Lead sponsor: TeneoOne Inc.
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2019-05-01
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Dose-limiting toxicities (DLT)
timeFrame: Day 21
measure: Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs)
timeFrame: Up to 3 Years
measure: Maximum Observed Plasma Concentration of TNB-383B (Cmax)
timeFrame: Week 12
measure: Time to Cmax of TNB-383B (Tmax)
timeFrame: Week 12
measure: Area Under the Concentration Versus Time Curve from Time Zero to the Last Measurable Concentration (AUClast)
timeFrame: Week 12
measure: Clearance (CL) of TNB-383B
timeFrame: Week 12
measure: Terminal Phase Elimination Rate Constant (Beta) of TNB-383B
timeFrame: Week 12
measure: Terminal Half-Life (t1/2) of TNB-383B
timeFrame: Week 12
measure: Number of Participants with of Anti-drug Antibody (ADA)
timeFrame: Up to Month 48
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to Month 48
measure: Percentage of Participants with Overall Survival (OS)
timeFrame: Up to 48 Months
measure: Percentage of Participants with Progression-Free Survival (PFS)
timeFrame: Up to 48 Months
measure: Time-to-Progression (TTP)
timeFrame: Up to 48 Months
measure: Time-to-Response (TTR)
timeFrame: Up to 48 Months
measure: Duration of Objective Response (DOR)
timeFrame: Up to 48 Months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) - Parnassus Heights /ID# 238680
state: California
city: New Orleans
country: United States
facility: Tulane University School of Medicine /ID# 242322
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic - Rochester /ID# 238683
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 238681
state: Missouri
city: New York
country: United States
facility: Mt Sinai /ID# 242317
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina /ID# 238685
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute /ID# 238786
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Univ HS /ID# 238787
state: North Carolina
city: Milwaukee
country: United States
facility: Wisconsin Medical Center /ID# 238684
state: Wisconsin
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln /ID# 239676
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: Duplicate_Universitaetsklinikum Muenster /ID# 239637
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 239638
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf /ID# 239636
Study officials:
affiliation: TeneoOne Inc.
name: TeneoOne Inc
role: STUDY_DIRECTOR
References:
citation: 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.