LAUSANNE, Switzerland — ADC Therapeutics SA (NYSE: ADCT) today announced that initial data from an investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA® (loncastuximab tesirine-lpyl) demonstrated a high response rate in patients with relapsed/refractory (r/r) marginal zone lymphoma (MZL).
The 50-patient single-arm, open-label Phase 2 multicenter study is currently being conducted at the Sylvester Comprehensive Cancer Center at University of Miami and City of Hope, and led by Izidore Lossos, MD, Professor, Director, Lymphoma Program at the Sylvester Comprehensive Cancer Center, University of Miami. This study is evaluating the safety and efficacy of six cycles of ZYNLONTA across 18 weeks in patients with r/r MZL previously treated with ≥1 line of systemic therapy (ClinicalTrials.gov identifier: NCT05296070). As of the data cutoff date of March 30, 2024, 15 patients were evaluable. Of these 15 patients evaluated, 13 achieved a complete response (CR) and one patient achieved a partial response (PR). All patients who achieved responses had maintained them at the time of the data cutoff.
In this study, ZYNLONTA was generally well-tolerated and safety was consistent with the known profile, with two patient discontinuations. One patient discontinued after cycle 2 and a second patient discontinued after cycle 4 due to a toxicity, which fully resolved upon discontinuation of treatment. Both of these patients remain in CR at 10 and 6 months, respectively.
These initial data were presented at the Lymphoma Research Foundation’s 2024 Marginal Zone Lymphoma Scientific Workshop by the trial’s lead investigator, Izidore Lossos, MD, Professor, Director, Lymphoma Program at the Sylvester Comprehensive Cancer Center, University of Miami.
“Achievement of complete response to treatment represents the strongest predictor of positive outcomes in MZL so these initial results are encouraging,” said Dr. Lossos. “We are now expanding the number of sites to accelerate enrollment in this trial.”
MZL is a rare, indolent non-Hodgkin lymphoma (NHL) and the third most common NHL subtype. There are few FDA-approved therapies for MZL.
“Relapsed/refractory MZL can be difficult to manage, making this an indication of high unmet medical need,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “As this investigator-initiated trial progresses, assuming the results continue to be positive, we plan to potentially pursue a regulatory pathway and compendia in parallel as soon as sufficient data are available.”
“Approximately 3,000 to 4,000 relapsed/refractory MZL patients are treated in the U.S. annually,” said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. “Based on the initial data from University of Miami’s Phase 2 trial evaluating ZYNLONTA in relapsed/refractory MZL, we are encouraged by the potential opportunity in the 2L+ setting for patients with this rare disease.”
About ZYNLONTA® (loncastuximab tesirine-lpyl)
ZYNLONTA® is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized 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 tumor cell death.
The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (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. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.
ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.
About ADC Therapeutics
ADC Therapeutics (NYSE: ADCT) is a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs). The Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.
ADC Therapeutics’ CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development.
ADC Therapeutics is based in Lausanne (Biopôle), Switzerland and has operations in London and New Jersey.
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