Benzinga | Jul 17, 2020 07:17AM EDT

ADC Therapeutics Announces First Patient Dosed In Pivotal Phase 2 Portion Of LOTIS 3 Clinical Trial Of Loncastuximab Tesirine (Lonca) In Combination With Ibrutinib

Combination is being evaluated in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL)

Trial is intended to support the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA)

ADC Therapeutics SA (NYSE:ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, today announced that the first patient has been dosed in the pivotal Phase 2 portion of LOTIS 3, a Phase 1/2 clinical trial evaluating loncastuximab tesirine (Lonca, formerly ADCT-402) in combination with ibrutinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL).

"Based on the encouraging interim data Lonca and ibrutinib demonstrated in Phase 1, the trial was amended to a Phase 1/2 protocol intended to support the submission of a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA)," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "We are pleased to have dosed the first patient in the pivotal Phase 2 portion of this trial as we continue advancing Lonca as both a single agent and in combination with other therapies for patients with non-Hodgkin lymphoma. We are on track to file a BLA with the FDA for Lonca as monotherapy for the treatment of relapsed or refractory DLBCL in the second half of 2020."

The 161-patient Phase 1/2 open-label, single-arm clinical trial is evaluating the safety and efficacy of Lonca in combination with ibrutinib in patients with relapsed or refractory DLBCL or MCL. The Phase 2 portion of the trial will enroll three cohorts: non-germinal center B-cell-like (non-GCB) DLBCL, GCB DLBCL and MCL.

"A significant proportion of patients with non-Hodgkin lymphoma relapse after treatment and their prognosis is poor, underscoring the need for new options for later-lines of therapy," said Murali Janakiram, MD, MS, Assistant Professor of Medicine, University of Minnesota, Division of Hematology, Oncology, and Transplantation, and an investigator for the trial. "The combination of Lonca, a CD19-targeted ADC, and ibrutinib, a small-molecule inhibitor of Bruton's tyrosine kinase, has shown synergy and I look forward to its continued evaluation in patients with relapsed or refractory DLBCL or MCL."

Interim data from the Phase 1 portion of the Phase 1/2 clinical trial presented at the virtual 25th Congress of the European Hematology Association in June 2020 showed an overall response rate of 75.0% and complete response rate of 58.3% at the Lonca dose of 60 ?g/kg, which is the selected dose for the Phase 2 portion of the trial, in combination with ibrutinib (560 mg/day) in patients with relapsed or refractory DLBCL or MCL. The combination has had a manageable toxicity profile, with the most common grade ?3 treatment-emergent adverse events in ?10% of patients being thrombocytopenia (20%) and anemia (12%).