Mantle cell lymphoma

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."

"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.