Swiss pharmaceutical company ADC Therapeutics SA (NYSE:ADCT) on Wednesday announced topline data from its Phase 3 LOTIS-5 confirmatory trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).

According to the company, ZYNLONTA plus rituximab achieved statistical significance on the trial's primary endpoint of progression-free survival (PFS) and demonstrated no detrimental effect on the key secondary efficacy endpoint of overall survival (OS). In addition, a higher complete response (CR) rate and duration of CRs (DoCR) were observed with ZYNLONTA plus rituximab. Overall, treatment emergent adverse event (TEAE) rates were similar between arms. Similar rates of overall Grade 3 or higher TEAEs greater than 5% were observed across both arms, with haematologic TEAEs higher in the control arm and infection, hepatotoxicity, and oedema/effusion higher in the test arm. Serious adverse events (SAEs), TEAEs leading to study drug withdrawal, and Grade 5 events were higher in the test arm, with the majority of Grade 5 TEAEs in the test arm occurring in patients aged 75 years or older.

The LOTIS-5 trial is a randomised, open-label, two-arm, multicentre study evaluating ZYNLONTA plus rituximab versus the standard immunochemotherapy rituximab gemcitabine-oxaliplatin (R-GemOx), for the treatment of r/r DLBCL after one or more lines of systemic therapy. The study met the primary endpoint of PFS with statistical significance, with a median PFS of 6.1 months for ZYNLONTA plus rituximab vs 4.7 months for R-GemOx.

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalised by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumour cell death.

The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with r/r large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.