A Phase 1 trial evaluating Teneobio’s bispecific antibody TNB-383B as a treatment for multiple myeloma has started dosing patients. This safety and tolerability trial is recruiting people with advanced disease, who received at least three prior lines of therapy.
The open-label study (NCT03933735) will first test increasing doses of TNB-383B, delivered into the bloodstream every three weeks, in 24 people with relapsed or refractory multiple myeloma. After an optimal dose has been found, an additional 48 patients will be enrolled to continue studying safety, and preliminary signs of efficacy using that dose.
It will also assess the therapy’s pharmacokinetics and pharmacodynamics — how the medicine acts and is processed in the body.
In total, 72 patients will be recruited at different locations across the United States. So far, only sites in North Carolina and Wisconsin are recruiting patients, with four other sites expected to open soon.
TNB-383B is an antibody that acts as a bridge between immune cells and cancer cells by binding to proteins located on the surface of both cell types. Specifically, TNB-383B binds to the CD3 surface receptor on the immune T-cells, and to the B-cell maturation antigen (BCMA) on myeloma cells, the company states.
This brings T-cells closer to cancer cells, enabling them to destroy multiple myeloma cells, while reducing the release of specific signaling molecules (known as cytokines) from activated T-cells— a process that causes most adverse events in immunotherapies.
Preclinical studies have tested TNB-383B in mouse models of myeloma. The treatment was seen to prevent tumor growth, eliminate myeloma cells, and lead to a diminished production of inflammatory molecules compared to other two-target antibodies, the reason it is believed to carry fewer side effects.
TNB-383B used on bone marrow samples from relapsed multiple myeloma patients was reported to result in a dose-dependent activation of T-cells and the death of multiple myeloma cells.
“Redirecting T-cells to kill cancer cells is a powerful therapeutic approach in the immuno-oncology space. We designed TNB-383B to efficiently kill multiple myeloma cells expressing BCMA and minimize cytokine release from CD3-activated T-cells. This latter attribute is a hallmark of our unique T-cell CD3 engaging therapeutic platform, which is in a number of our follow-on programs and lead clinical candidates,” Roland Buelow, CEO of Teneobio, said in a press release.
“Our new class of T-cell engagers were designed to increase the therapeutic window as monotherapies and they may also afford the opportunity for combination treatments of patients,” Buelow added.
Under a collaboration established with AbbVie, Teneobio, and its affiliate TeneoOne this year, AbbVie may opt to acquire TNB-383B after Phase 1 studies conclude to continue its development and potential commercialization.