On June 29, 2022, ADC Therapeutics announced that it has completed the first patient dosing of Zynlonta in the Phase 1b LOTIS-7 trial evaluating combination with other anticancer agents for relapsed or refractory B-cell non-Hodgkin lymphoma patient outcomes. LOTIS-7 is an open-label, multicenter, multi-arm trial evaluating Zynlonta in combination with polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (including diffuse large B-cell lymphoma, high-grade B-cell lymphoma tumor, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma); the trial will consist of two parts, a dose-escalation and a dose-expansion part.
“Because Zynlonta has shown synergistic or additive effects in preclinical studies with other anticancer therapies, we are eager to further explore the potential of CD19-targeted ADCs in combination with other therapies,” said Joseph, Chief Medical Officer, ADC Therapeutics. “We look forward to enabling more patients with lymphoma to respond and benefit from the new combination assessment in the LOTIS-7 trial,” said Dr. Camardo.
Zynlonta (loncastuximab tesirine) is an ADC composed of a humanized monoclonal antibody targeting CD19 coupled to a cytotoxin-pyrrolobenzodiazepine (PBD) dimer. When bound to CD19-expressing cancer cells, Zynlonta is endocytosed and taken up by cancer cells and subsequently releases a toxic warhead that kills the cancer cells. In April 2021, the FDA approved Zynlonta as the first CD19-targeted ADC as a monotherapy for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) who have undergone second- or multiple-line systemic therapy. Currently, Zynlonta has been approved by the European Medicines Agency (EMA) for a Marketing Authorization Application (MAA) and is under review by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
The U.S. approval of Zynlonta is data from the pivotal Phase 2 clinical trial LOTIS 2, a multicenter, open-label, single-arm clinical study evaluating the efficacy and safety of Zynlonta in ≥2-line treatment of r/r DLBCL. The study showed that the overall response rate (ORR) was 48.3% (70/145), and the complete response rate (CR) was 24.1% (35/145); the median response time of patients was 1.3 months, of which 70 responders had The median duration of response (mDoR) was 10.3 months. In terms of safety, ≥10% of patients had treatment-emergent adverse events of grade ≥3. The most common treatment-emergent adverse events of grade ≥3 were neutropenia, febrile neutropenia, thrombocytopenia, Increased GGT and anemia.