Description:
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 subjects with
relapsed or refractory MM who have received at least 3 prior lines of therapy. The study
consists of 2 portions, a monotherapy dose escalation (Arm A) and a monotherapy dose
expansion (Arm B). Arm A will evaluate the safety, tolerability, PK and PD profiles of
escalating doses of single-agent TNB-383B, administered once every 3 weeks (Q3W), in
approximately 85 subjects. 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, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the MTD/RP2D dose of
TNB 383B monotherapy in approximately 48 subjects.
Title
- Brief Title: A Study of TNB-383B in Subjects 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
Clinical Trial IDs
- ORG STUDY ID:
TNB383B.0001
- NCT ID:
NCT03933735
Conditions
Interventions
Drug | Synonyms | Arms |
---|
TNB-383B | | Arm A: Dose Escalation |
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 subjects with
relapsed or refractory MM who have received at least 3 prior lines of therapy. The study
consists of 2 portions, a monotherapy dose escalation (Arm A) and a monotherapy dose
expansion (Arm B). Arm A will evaluate the safety, tolerability, PK and PD profiles of
escalating doses of single-agent TNB-383B, administered once every 3 weeks (Q3W), in
approximately 85 subjects. 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, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the MTD/RP2D dose of
TNB 383B monotherapy in approximately 48 subjects.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: Dose Escalation | Experimental | Up to 15 cohorts of subjects receiving sequentially ascending doses of TNB-383B are planned until maximum tolerated dose is reached or recommended phase 2 dose is identified. | |
Arm B: Dose Expansion | Experimental | An expansion cohort will be enrolled after maximum tolerated dose or recommended phase 2 dose is established. | |
Eligibility Criteria
Inclusion Criteria:
- Subjects with Relapsed/Refractory Multiple Myeloma.
- Subject 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 (e.g., daratumumab).
- Subject 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).
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Prior bone marrow transplant is acceptable if subject is > 12 weeks (autologous) or >
1 year (allogeneic) status-post transplantation
- Subject must have adequate bone marrow function, defined as:
- absolute neutrophil count (ANC) ≥ 1000/mm3;
- platelets ≥ 50,000/mm3;
- hemoglobin ≥ 8.0 g/dL.
- Subject must have an eGFR ≥ 30 mL/min as estimated by the MDRD formula.
- Subject 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.
Exclusion Criteria:
- Subject has ever received BCMA-targeted therapy. Subjects who have received targeted
therapy against non-BCMA targets will not be excluded
- Subject has a history of central nervous system involvement by their myeloma.
- Subject has a history of ≥ Grade 3 peripheral neuropathy.
- Subject has a history of plasma cell leukemia, POEMS syndrome, or amyloidosis.
- Subject 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.
- Subject has a history of major cardiac abnormalities.
- Subject has a known active infection requiring parenteral anti-infective treatment
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of subjects with Dose-limiting toxicities (DLT) |
Time Frame: | 21 days |
Safety Issue: | |
Description: | The incidence, timing, seriousness, and relationship to study treatments of adverse events will be evaluated. An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. |
Secondary Outcome Measures
Measure: | Incidence of Anti-drug Antibody (ADA) |
Time Frame: | 48 months |
Safety Issue: | |
Description: | The number of participants with anti-TNB-383B antibodies |
Measure: | Titers of Anti-drug Antibody (ADA) |
Time Frame: | 48 months |
Safety Issue: | |
Description: | The titers of anti-TNB-383B antibodies |
Measure: | Anti-Myeloma Activity by Objective Response Rate (ORR) |
Time Frame: | 48 months |
Safety Issue: | |
Description: | The objective response rate, defined as the proportion of subjects with a confirmed partial (PR) or complete (CR) response to treatment as determined using International Myeloma Working Group (IMWG) uniform response criteria |
Measure: | Anti-Myeloma Activity by Duration of Objective Response (DOR) |
Time Frame: | 48 months |
Safety Issue: | |
Description: | Duration of objective response is measured as the time from the initial objective response to disease progression or death, whichever occurs first. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Teneobio, Inc. |
Last Updated
December 19, 2020