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

• Sponsor: TeneoOne Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03933735
• Collaborator: AbbVie (Industry)
• Enrollment: 214
• Locations: 15
• Arms: 5
• Anticipated Duration (Months): 74
• Patients Per Site: 14.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: TNB-383B	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 214 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 24, 2019
• Anticipated Primary Completion Date: Aug 24, 2025
• Anticipated Study Completion Date: Aug 24, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants with Dose-limiting toxicities (DLT) [Day 21]

   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.

2. Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) [Up to 3 Years]

   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.

3. Maximum Observed Plasma Concentration of TNB-383B (Cmax) [Week 12]

   Cmax of TNB-383B.

4. Time to Cmax of TNB-383B (Tmax) [Week 12]

   Time to maximum plasma concentration (Tmax) of TNB-383B.

5. Area Under the Concentration Versus Time Curve from Time Zero to the Last Measurable Concentration (AUClast) [Week 12]

   Area under the concentration versus time curve from time zero to the last measurable concentration of TNB-383B.

6. Clearance (CL) of TNB-383B [Week 12]

   Clearance is defined the volume of plasma cleared of the drug per unit time.

7. Terminal Phase Elimination Rate Constant (Beta) of TNB-383B [Week 12]

   Apparent terminal phase elimination rate constant of TNB-383B.

8. Terminal Half-Life (t1/2) of TNB-383B [Week 12]

   Terminal half-life (t1/2) of TNB-383B.

9. Number of Participants with of Anti-drug Antibody (ADA) [Up to Month 48]

   The number of participants with anti-TNB-383B antibodies.

Secondary Outcome Measures

1. Objective Response Rate (ORR) [Up to Month 48]

   ORR is defined as confirmed Stringent complete response (sCR) + Complete response (CR) + very good partial response + partial response [PR]).

2. Percentage of Participants with Overall Survival (OS) [Up to 48 Months]

   OS is defined as time from the first dose of TNB-383B to the date of death, from any cause.

3. Percentage of Participants with Progression-Free Survival (PFS) [Up to 48 Months]

   Progression-free survival time is defined as the time from the first dose of TNB-383B to progression or death, whichever occurs first.

4. Time-to-Progression (TTP) [Up to 48 Months]

   TTP is defined as the time from the first dose of TNB-383B to the date of the first documented disease progression.

5. Time-to-Response (TTR) [Up to 48 Months]

   TTR is defined as the time from the first dose of TNB-383B to the date of the first assessment having documented the response.

6. Duration of Objective Response (DOR) [Up to 48 Months]

   DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco Medical Center /ID# 238680	San Francisco	California	United States	94143-0324
2	Tulane University /ID# 242322	New Orleans	Louisiana	United States	70112-2699
3	Mayo Clinic - Rochester /ID# 238683	Rochester	Minnesota	United States	55905-0001
4	Washington University-School of Medicine /ID# 238681	Saint Louis	Missouri	United States	63110
5	Mt Sinai /ID# 242317	New York	New York	United States	10029
6	Memorial Sloan Kettering Cancer Center-Koch Center /ID# 244831	New York	New York	United States	10065-6007
7	University of North Carolina /ID# 238685	Chapel Hill	North Carolina	United States	27514
8	Levine Cancer Ins, Carolina Me /ID# 238786	Charlotte	North Carolina	United States	28204
9	Wake Forest Univ HS /ID# 238787	Winston-Salem	North Carolina	United States	27157
10	Houston Methodist Hospital /ID# 242329	Houston	Texas	United States	77030
11	Medical College of Wisconsin /ID# 238684	Milwaukee	Wisconsin	United States	53226-3522
12	Universitaetsklinikum Koeln /ID# 239676	Köln	Nordrhein-Westfalen	Germany	50937
13	Universitaetsklinikum Muenster /ID# 239637	Muenster	Nordrhein-Westfalen	Germany	48149
14	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 239638	Dresden		Germany	01307
15	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 239636	Hamburg		Germany	20246

Sponsors and Collaborators

• TeneoOne Inc.
• AbbVie

Investigators

• Study Director: TeneoOne Inc, TeneoOne Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TeneoOne Inc.
• ClinicalTrials.gov Identifier: NCT03933735
• Other Study ID Numbers: TNB383B.0001; 2020-000199-40
• First Posted: May 1, 2019
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by TeneoOne Inc.: Multiple Myeloma; TNB-383B
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

No Results Posted as of Aug 23, 2022