Positive results from the pivotal 145-patient phase 2 clinical trial of Loncastuximab tesirine ( ADCT-402 ) for the treatment of relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ) were announced.
Loncastuximab tesirine has achieved an overall response rate ( ORR ) of 45.5% ( 66/145 patients ), including 20% complete responses and 25.5% partial responses, across a broad population of relapsed or refractory DLBCL patients, even those who are difficult to treat.
Comparably, the ORR in the 183-patient phase 1 clinical trial of Loncastuximab tesirine at the initial dose used in phase 2 was 41.4% ( 29/70 patients ), including 21.4% complete responses and 20% partial responses.
Loncastuximab tesirine has demonstrated manageable toxicity in patients with relapsed or refractory DLBCL.
The most common grade greater than or equal to 3 treatment-emergent adverse events in the phase 2 clinical trial were neutropenia, thrombocytopenia and increased gamma-glutamyltransferase.
These data have exceeded the primary endpoint target and have reinforced the significant single-agent anti-tumor activity and manageable toxicity profile of Loncastuximab tesirine in patients with relapsed or refractory DLBCL who have failed established therapies.
The single-arm, multi-center, open-label, trial has evaluated the safety, efficacy and pharmacokinetics of Loncastuximab tesirine as a monotherapy in patients with relapsed or refractory DLBCL.
Patients received 30-minute intravenous infusions of Loncastuximab tesirine once every three weeks at a dose of 150 μg/kg for the first two cycles, followed by 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first.
Loncastuximab tesirine is an antibody drug conjugate ( ADC ) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine ( PBD ) dimer cytotoxin.
Once bound to a CD19-expressing cell, Loncastuximab tesirine is designed to be internalized by the cell, following which the warhead is released. The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death.
CD19 is a clinically validated target for the treatment of B-cell malignancies. ( Xagena )
Source: ADC Therapeutics, 2020