TNB-383B is a bi-specific antibody, meaning that it interacts with two molecules in your body. One molecule is called B-Cell Maturation Antigen (BCMA) and is found on your multiple myeloma cells. The second is called CD3 and is present on your killer T-cells. When CD3 is engaged on a T cell, it turns the T-cell on and makes it kill whatever cell triggered the activation. Because TNB-383B sticks very strongly to the BCMA on your myeloma cells, nearby T-cells should specifically attack your tumor cells.
This study is open-label, meaning that everyone on the study will receive TNB-383B. It is a Phase 1, First-in-Human trial, meaning that it is the first study where TNB-383B will be given to human patients. TNB-383B is an investigational agent, meaning that it is still being tested for safety and efficacy and has not yet been approved by the FDA.
The purpose of the Study is:
This trial is currently open and accepting patients.
The study is divided into two parts. Part 1 of the Study will be conducted with approximately 24 participants at about 6 sites in the United States.
This first part will test different and increasing doses of TNB-383B. In Part 1 of the study, called the “dose escalation phase”, approximately 9 different, increasing doses of TNB-383B will be tested. TNB-383B is a medication that is given to you in the doctor’s office by an intravenous injection(IV, which means in the arm vein or central line). Each dose of TNB-383B will be assigned to a separate group of 1-6 participants. If the group assigned to the first dose level tolerates TNB-383B without serious side effects, then the next group will be assigned an increased dose of TNB-383B. This will continue until pre-determined and/or significant side effects are seen or the highest planned dose has been tested. The Sponsor will then stop the dose escalation part of the Study and move into the next part of the study, called the “expansion” phase.
The total number of patients enrolled in both arms of the study is anticipated to be approximately 72 subjects. This includes approximately 24 patients in the dose escalation arm and approximately 48 patients in the dose expansion arm of the study,
TNB-383B is a medication that is given to you in the doctor’s office by an intravenous injection(IV, which means in the arm vein or central line). After the first dose, a patient receiving TNB-383B must stay in the hospital for 48 hours to let the doctors observe them for any reaction they might have to the drug.
Your time in this research study will be followed in cycles. One cycle is 21 days (3 weeks) in duration. The duration of participation in this study may be different for each participant. For most participants, the screening will take up to 28 days to determine if you meet all of the criteria for study participation, called eligibility. If you are eligible to participate in this study, you will be enrolled and receive TNB-383B once every three weeks. Study participants will be given TNB-383B and carefully monitored for as long as your myeloma is not growing, you do not have any unacceptable side effects, and you do not decide to withdraw from the study.
This study includes four periods:
If at any point you become unwell during the study, either from your myeloma, another illness/injury, or from side effects of your medications, it may require additional, unscheduled visits or possibly even a hospital admission. Your safety and well-being are our first priority so you may be asked to come in for an office visit or be admitted to the hospital at a lower threshold than you are used to while not receiving an investigational agent. You are always encouraged to let your Study doctor know if you have concerns or are feeling unwell. Nevertheless, your Study doctor will also strive to minimize inconvenience and disruption for you.
If your myeloma gets worse despite treatment with TNB-383B, or if you have a bad reaction to TNB-383B that the doctors cannot effectively treat, TNB-383B will likely be stopped. However, your Study doctor or nurse will continue to check in via telephone with you every 3 months to see how you are doing.
Study visits and evaluations will be performed at Screening and at Day 1 of each Cycle. Based on a 3- week cycle, additional study visits and evaluations will be performed on Days 2, 3, 8, and 15 during the first Cycle, on Day 15 only in Cycles 2 and 3, and on Days 2, 8, and 15 in Cycle 6.
The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.
You may be eligible to participate in this study if you:
Enrollment: 133 patients (estimated)View More
December 13, 2021
As of 10 May 2021, 103 pts (dose escalation, n=73; dose expansion, n=30) have been treated with TNB-383B (0.025–120 mg). The RP2D of 60 mg Q3W was selected on the basis of tolerability, safety, PK, and clinical activity. Pt demographics and baseline characteristics are summarized in Table 1. Three dose-limiting toxicities were reported in dose escalation (platelet count decreased: grade [Gr] 4, 60 mg; cytokine release syndrome [CRS]: Gr 3, 90 mg and 120 mg); none were reported as serious.
Treatment-related AEs (TRAEs) were reported in 79 (77%) pts, with Gr ≥3 and serious AEs occurring in 33 (32%) and 23 (22%) pts, respectively. The most common TRAEs (Table 2) include CRS (n=54, 52%), neutropenia (n=18, 17%), and fatigue (n=14, 14%). At the RP2D (n=39), the Gr ≥3 CRS rate was 3% (n=1). Onset of CRS typically occurred on the same or next day following the first dose and all pts recovered using tocilizumab or standard supportive care measures. Treatment-emergent AEs (TEAEs) of infusion-related reactions were reported in 8 (8%) pts and infections occurred in 29 (28%) pts; pneumonia (n=5, 5%) and upper respiratory tract infection (n=4, 4%) were the most common. Five deaths from TEAEs were reported; all were unrelated to study drug. Forty-two (40%) pts discontinued treatment due to disease progression.
In the dose-escalation cohorts of ≥40 mg Q3W (n=24), the objective response rate (ORR) was 79% (19/24), with a very good partial response or better (≥VGPR) rate of 63% (15/24), and a complete response (CR) rate of 29% (7/24) at the data cutoff date; these pts have the longest follow-up (ie, mature data) with median time on study of 6.1 months (Figure 1). At doses ≥40 mg in the combined dose-escalation and -expansion cohorts (n=44), the observed ORR, ≥VGPR, and CR rates were 64% (28/44), 43% (19/44), and 16% (7/44), respectively; these pts have shorter follow-up (ie, immature data) with median time on study of 3.1 months. Twenty-nine (66%) of the 44 pts administered ≥40 mg were triple-class refractory and reported an ORR of 55% (16/29).
December 06, 2020
A novel BCMA and CD3 targeted bispecific T-cell engaging immunotherapy agent TNB-383B has demonstrated significant responses at higher dose levels and tolerability at all dose levels, including mild cases of cytokine release syndrome (CRS), according to initial results of a phase 1 trial (NCT03933735) presented during the 2020 American Society of Hematology (ASH) Annual Meeting.
CRS was the most common adverse event (AE) reported on the study and was observed in 45% of patients at any grade, which increased to 80% in patients who received doses ≥40 mg, but cases were grade 1/2. The median onset to CRS was less than a day (range, 0-7) and the median duration was 1 day (range, 1-7). Five patients were treated with tocilizumab. Only 1 patient had a reoccurrence of CRS.
Other common AEs included fatigue (24%), headache (22%), infection (21%), nausea (21%), and anemia (21%). The most common grade ≥3 AEs were anemia (17%), neutropenia (16%), thrombocytopenia (14%), and infection (14%). Treatment-related AEs increased at higher doses ≥40 mg due to increased CRS, but there was no significant increase observed in the incidence of other AEs with higher doses of treatment.
The objective response rate (ORR) at lower doses (0.025 to 1.8 mg; n = 15) was 20%, with a complete response (CR) rate or better of 6.7%. At doses from 5.4 to 30 mg (n = 28), the ORR was 43% with a CR or better rate of 17.9%. The ORR was 80% at higher dose levels (40 to 60 mg; n = 15) with a CR or better rate of 13.3%. Three of 4 patients evaluable for minimal residual disease were found to be negative.
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