A Study of TNB-383B in Subjects With Relapsed or Refractory Multiple Myeloma
Trial Status: Active
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 ranging from 25 micrograms to 40 milligrams per dose, administered once every 3 weeks (Q3W), in approximately 24 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.
- 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 (ie, 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.
- 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
UCSF Medical Center-Mount Zion
Contact: Helen Diller Family Comprehensive Cancer Center
Mayo Clinic in Rochester
Siteman Cancer Center at Washington University
Wake Forest University Health Sciences
Trial Phase Phase I
Trial Type Treatment
- Primary ID TNB383B.0001
- Secondary IDs NCI-2019-06571
- Clinicaltrials.gov ID NCT03933735