Phase 2 Trial Shows Promising ZYNLONTA® Results in Relapsed/Refractory MZL Patients

A recent clinical study has shed light on the potential of a novel antibody drug conjugate (ADC) in treating patients with relapsed/refractory (r/r) marginal zone lymphoma (MZL). The Phase 2 trial, initiated by investigators, utilized a CD19-directed ADC named ZYNLONTA® (loncastuximab tesirine-lpyl) and yielded promising results. Out of the 15 patients assessed, 13 experienced a complete response, and one patient had a partial response, indicating a robust response rate to the treatment.
The study, which is still ongoing, is being conducted at prestigious medical centers, including the Sylvester Comprehensive Cancer Center at the University of Miami and City of Hope. It is led by Dr. Izidore Lossos, a renowned expert in the field of lymphoma. The trial focuses on the evaluation of ZYNONTA's safety and efficacy over a period of 18 weeks in patients who have undergone at least one prior systemic therapy regimen. As of March 30, 2024, the data from the first 15 patients showed that all who responded to the treatment were still in remission at the time of the data cutoff.
ZYNONTA® was found to be generally well-tolerated by the patients, with its safety profile aligning with what is already known about the drug. Notably, two patients had to discontinue the treatment due to toxicity, but both recovered fully upon cessation and remained in complete remission at the time of reporting.
The positive preliminary findings were presented at a scientific workshop organized by the Lymphoma Research Foundation in 2024 by the principal investigator, Dr. Lossos. He emphasized the significance of achieving a complete response in MZL, as it is a strong indicator of favorable outcomes. The study team is now looking to expand the trial to include more sites and accelerate patient enrollment.
MZL is a rare form of non-Hodgkin lymphoma (NHL) and is the third most common subtype of NHL. There are limited FDA-approved treatments available for MZL, making the development of new therapeutic options crucial. Dr. Mohamed Zaki, the Chief Medical Officer of ADC Therapeutics, highlighted the high unmet medical need for r/r MZL and the company's intention to pursue regulatory approval and inclusion in compendia as the trial progresses positively.
ADC Therapeutics, a commercial-stage company and a pioneer in ADC technology, is committed to transforming cancer treatment for patients with hematologic malignancies and solid tumors. Their flagship product, ZYNLONTA, has received accelerated approval from the FDA and conditional approval from the European Commission for the treatment of r/r large B-cell lymphoma after two or more lines of systemic therapy. The company is also exploring ZYNLONTA's potential in combination therapies and earlier lines of treatment for B-cell malignancies.
ZYNONTA® works by targeting CD19-expressing cells and releasing a potent pyrrolobenzodiazepine (PBD) payload that binds to DNA, leading to cell cycle arrest and tumor cell death. The drug's mechanism of action and its approval for specific patient populations underscore the innovation in targeted cancer therapies. ADC Therapeutics, headquartered in Switzerland with operations in London and New Jersey, continues to advance its proprietary ADC technology, aiming to improve patient outcomes in the fight against cancer.