Swiss drug discovery company ADC Therapeutics has commenced dosing patients in a Phase I clinical trial assessing its ADCT-402 (loncastuximab tesirine) in combination with AstraZeneca’s Imfinzi (durvalumab) for advanced non-Hodgkin lymphoma.
The trial will involve patients with advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL).
ADCT-402 is an antibody drug conjugate (ADC) being developed to target and destroy CD19-expressing malignant B-cells.
Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80 in order to prevent the tumour’s immune-evasion and release the inhibition of immune responses.
The open-label, single-arm Phase I trial will assess the safety, tolerability, pharmacokinetics and anti-tumour activity of the combination in around 75 patients.
It will comprise a dose escalation and a dose expansion part. The dose escalation portion will involve a standard 3+3 design, while the dose expansion phase will involve one cohort each for DLBCL, MCL and FL in order to evaluate additional safety and preliminary anti-tumour activity at the maximum tolerated dose.
Primary outcome measures of the trial are frequency and severity of serious adverse events, as well as the incidence of dose-limiting toxicities.
The study’s secondary outcome measures include overall response rate (ORR), complete response rate, duration of response and overall survival.
ADC Therapeutics clinical development chief medical officer and senior vice-president Jay Feingold said: “Data from our 183-patient first-in-human clinical trial of ADCT-402, which were presented at the 60th American Society of Hematology (ASH) Annual Meeting, demonstrated its acceptable safety profile and promising anti-tumour activity as a single agent in patients with relapsed or refractory B-cell non-Hodgkin lymphomas.
“We are now excited to explore the possible impact of ADCT-402 plus durvalumab in patient populations that would greatly benefit from new treatment options.”
The Phase I 183-patient trial demonstrated manageable toxicity in a subpopulation of 139 relapsed or refractory DLBCL patients who failed or were intolerant to existing therapies.