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

Study Purpose

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 Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03933735
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

TeneoOne Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

TeneoOne Inc
Principal Investigator Affiliation TeneoOne Inc.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Germany, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Arms & Interventions

Arms

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.

Experimental: Arm B: Dose Expansion Dose A

An expansion cohort will be enrolled at the recommended phase 2 Dose A.

Experimental: Arm B: Dose Expansion Dose B

An expansion cohort will be enrolled at the recommended phase 2 Dose B.

Experimental: Arm E: Monotherapy Once Every 4 Weeks (Q4W)

An expansion cohort will be enrolled at the recommended phase 2 Dose A.

Experimental: Arm F: Monotherapy Dose C

An expansion cohort will be enrolled at the recommended phase 2 Dose C.

Interventions

Drug: - TNB-383B

Intravenous (IV) Injection

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

San Francisco, California

Status

Recruiting

Address

University of California San Francisco Medical Center /ID# 238680

San Francisco, California, 94143-0324

Tulane University /ID# 242322, New Orleans, Louisiana

Status

Recruiting

Address

Tulane University /ID# 242322

New Orleans, Louisiana, 70112-2699

Mayo Clinic - Rochester /ID# 238683, Rochester, Minnesota

Status

Recruiting

Address

Mayo Clinic - Rochester /ID# 238683

Rochester, Minnesota, 55905-0001

Saint Louis, Missouri

Status

Recruiting

Address

Washington University-School of Medicine /ID# 238681

Saint Louis, Missouri, 63110

Mt Sinai /ID# 242317, New York, New York

Status

Not yet recruiting

Address

Mt Sinai /ID# 242317

New York, New York, 10029

New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831

New York, New York, 10065-6007

University of North Carolina /ID# 238685, Chapel Hill, North Carolina

Status

Recruiting

Address

University of North Carolina /ID# 238685

Chapel Hill, North Carolina, 27514

Charlotte, North Carolina

Status

Recruiting

Address

Levine Cancer Ins, Carolina Me /ID# 238786

Charlotte, North Carolina, 28204

Wake Forest Univ HS /ID# 238787, Winston-Salem, North Carolina

Status

Recruiting

Address

Wake Forest Univ HS /ID# 238787

Winston-Salem, North Carolina, 27157

Houston Methodist Hospital /ID# 242329, Houston, Texas

Status

Not yet recruiting

Address

Houston Methodist Hospital /ID# 242329

Houston, Texas, 77030

Medical College of Wisconsin /ID# 238684, Milwaukee, Wisconsin

Status

Recruiting

Address

Medical College of Wisconsin /ID# 238684

Milwaukee, Wisconsin, 53226-3522

International Sites

Universitaetsklinikum Koeln /ID# 239676, Köln, Nordrhein-Westfalen, Germany

Status

Not yet recruiting

Address

Universitaetsklinikum Koeln /ID# 239676

Köln, Nordrhein-Westfalen, 50937

Muenster, Nordrhein-Westfalen, Germany

Status

Completed

Address

Universitaetsklinikum Muenster /ID# 239637

Muenster, Nordrhein-Westfalen, 48149

Dresden, Germany

Status

Recruiting

Address

Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 239638

Dresden, , 01307

Hamburg, Germany

Status

Recruiting

Address

Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 239636

Hamburg, , 20246