TNB-383B is a type of drug known as an immunotherapeutic drug. Immunotherapy is a form of cancer treatment that uses the immune system to attack cancer cells, similar to the way it attacks bacteria or viruses. This type of therapy works by activating immune cells circulating in your body. Simply put, immunotherapy is a tool to trigger your body to treat the cancer itself. TNB-383B has been developed in a laboratory to make powerful ‘killer’ T-cells from your own immune system attack multiple myeloma cells in your body.
TNB-383B is a ‘bispecific’ antibody, meaning that it interacts with two molecules in your body. One molecule is called B-Cell Maturation Antigen (BMCA) 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 your myeloma cells, nearby T-cells should specifically attack your tumor cells.
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.