Swiss firm ADC Therapeutics (ADCT) has started a Phase I trial of its antibody drug conjugate (ADC) ADCT-402 in patients with relapsed or refractory B-cell non-Hodgkin Lymphoma (B-NHL).
ADCT-402 is a combination of a humanised monoclonal antibody targeting the protein CD19 and a pyrrolo-benzodiazepine (PBD) warhead.
CD19 is a B-cell specific-surface protein expressed throughout B-cell development and on nearly all B-cell malignancies in many non-Hodgkin lymphomas.
CD19 has reportedly become an attractive target for ADC therapies due to its specificity.
The two stage, open-label trial is designed to evaluate the tolerability, safety, pharmacokinetics and activity of ADCT-402.
In the trial’s dose escalation phase, 30 patients will be enrolled at ten clinical sites across the US and EU.
This phase will determine the recommended dose of ADCT-402 for the second stage, which will aim to confirm the safety and efficacy profile for the drug at the selected dose.
ADC Therapeutics Clinical Development senior vice-president and CMO Dr Jay Feingold said: "Dosing the first patient in this trial with ADCT-402 is an important milestone for us and could pave the way for a better treatment regimen for patients.
"The trial will give us vital data on safety, tolerability, dosing and efficacy over the next two years.
"Following our pre-clinical studies suggesting ADCT-402 may also provide significant clinical benefit for patients suffering from lymphoblastic leukemia, we are exploring this potential further with a second study in patients with relapsed and / or refractory B-cell acute lymphoblastic leukemia now also open for patient recruitment."
The company noted that in pre-clinical in vivo models, ADCT-402 showed strong anti-tumour activity against CD19-positive leukemic and lymphoma cell lines at low single doses, outperforming other CD19-targeted ADCs currently indevelopment.
The company currently has two PBD-based ADCs undergoing four clinical trials, with other ADCs in pre-clinical development.
Image: Micrograph of mantle cell lymphoma, a type of non-Hodgkin lymphoma. Photo: courtesy of Nephron.