ADC Therapeutics Announces Updated ZYNLONTA® Investigator-Initiated Trial Data in R/R Marginal Zone Lymphoma Presented at 18th International Conference on Malignant Lymphoma (ICML)

Rhea-AI Summary

ADC Therapeutics announced updated Phase 2 trial data for ZYNLONTA in treating relapsed/refractory marginal zone lymphoma (r/r MZL) at ICML 2025. The trial showed impressive results with an 84.6% overall response rate and 69.2% complete response rate among 26 evaluable patients. Notably, 17 of 18 patients maintained complete response, with the longest duration being 27 months. The progression-free survival rate was 92.9% at 12 months. The treatment demonstrated a manageable safety profile, with mostly grade 1 or 2 adverse events. The study is expanding to additional sites to increase enrollment to 50 patients, and ADC Therapeutics plans to pursue regulatory pathways based on continued positive results.

Positive

• High overall response rate of 84.6% and complete response rate of 69.2% in r/r MZL patients
• Strong durability with 17 of 18 patients maintaining complete response, longest duration being 27 months
• Impressive 92.9% progression-free survival rate at 12 months
• Manageable safety profile with mostly grade 1-2 adverse events
• Study expansion to additional sites to accelerate enrollment

Negative

• Three patients required dose reduction due to adverse events
• One patient discontinued treatment due to cholestatic hepatitis
• Grade 3 and 4 adverse events observed in 18 patients total

Insights

Oncology Clinical Trials Specialist

ADCT's ZYNLONTA shows remarkable 85% response rate in marginal zone lymphoma, suggesting strong potential for label expansion.

The updated Phase 2 data for ZYNLONTA in relapsed/refractory marginal zone lymphoma (r/r MZL) demonstrates exceptional efficacy with an 84.6% overall response rate and 69.2% complete response rate. These numbers are particularly impressive for a heavily pre-treated lymphoma population. The durability of response is equally noteworthy, with 17 of 18 complete responders maintaining their response and the longest duration reaching 27 months.

The drug's efficacy in high-risk POD24 patients (those who progress within 24 months of initial therapy) is clinically significant, showing a 61.5% complete response rate in this traditionally difficult-to-treat subgroup. The 92.9% progression-free survival at 12 months further underscores ZYNLONTA's potential value in this indication.

The safety profile appears manageable and consistent with previous ZYNLONTA studies, with most adverse events being grade 1-2. While some grade 3-4 events occurred (neutropenia, RSV lung infection, hyponatremia), only one patient discontinued treatment due to an adverse event that fully resolved.

The expansion of trial sites to accelerate enrollment to 50 patients indicates confidence in these results and will provide a more robust dataset. The company's statement about potentially pursuing a regulatory pathway and compendia listing suggests they see a clear path forward for ZYNLONTA in MZL based on these encouraging results, which could significantly expand the drug's approved indications beyond its current use in diffuse large B-cell lymphoma.

Updated Phase 2 data evaluating ZYNLONTA^® as a monotherapy demonstrate overall response rate (ORR) of 85% and complete response (CR) rate of 69%

CR maintained in 17 of 18 patients who achieved CR, with longest duration of CR of 27 months from start of treatment

ZYNLONTA was generally well tolerated and safety was consistent with known profile

LAUSANNE, Switzerland, June 16, 2025 /PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced updated data from a Phase 2 multicenter investigator-initiated trial (IIT) of ZYNLONTA^® to treat relapsed/refractory marginal zone lymphoma (r/r MZL) will be presented during a poster session at the 18th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland on Friday, June 20. These data will be made available online beginning on Wednesday, June 18, at 8:30 a.m. CEST. The single-arm, open-label, study is led by Izidore S. Lossos, MD, Chief, Division of Hematology Lymphoma Section, at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

"These updated results further support the potential of ZYNLONTA as an effective single-agent treatment for patients with r/r MZL, including high-risk POD24 patients," said Lossos, the study's principal investigator. "Importantly, the treatment was generally well tolerated, with manageable safety consistent with the known profile."

As of February 10, 2025, a total of 27 adult patients with r/r MZL and previously treated with ≥1 line of systemic therapy were enrolled with 26 patients evaluable for response. Highlights of the data include:

• Overall response rate (ORR) of 84.6% (22/26); complete response (CR) rate of 69.2% (18/26)
• Among POD24 patients assessed for response, a CR rate of 61.5% (8/13) was observed
• CR was maintained in 17 of 18 CR patients who achieved CR, with longest duration of CR of 27 months from start of treatment
• Progression-free survival (PFS) was 92.9% at 12 months
• 27 enrolled patients experienced adverse events (AE), consistent with the known safety profile of ZYNLONTA and most commonly grade 1 or 2. Grade 3 and 4 AEs were observed in 16 and 2 patients, respectively and included neutropenia, RSV lung infection and hyponatremia (with 2 AEs occurring in the same patient). Three patients needed dose reduction and one patient discontinued treatment after cycle 4 due to cholestatic hepatitis that fully recovered.

The study is being conducted at Sylvester Comprehensive Cancer Center and at City of Hope, and recently expanded to Emory Winship Cancer Institute and Vanderbilt-Ingram Cancer Center to accelerate enrollment to 50 patients with r/r MZL. More details on this ongoing Phase 2 clinical trial can be found at https://clinicaltrials.gov/ (identifier: NCT05296070).

"Based on the updated Phase 2 IIT data to be shared at ICML, we are encouraged by the potential opportunity in r/r MZL and look forward to seeing additional data, as the trial expands to other sites." said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "As this 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."

In addition to the MZL poster presentation at ICML, an oral encore presentation of the LOTIS-7 Phase 1b open-label clinical trial evaluating the safety and efficacy of ZYNLONTA in combination with the bispecific antibody glofitamab (COLUMVI^®) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) will also be presented at ICML Friday, June 20 at 3:00 p.m. CEST.

About ZYNLONTA^® 

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 biotechnology company helping to improve the lives of those affected by cancer with its next-generation, targeted 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. For more information, please visit https://adctherapeutics.com/ and follow the Company on LinkedIn.

ZYNLONTA^® is a registered trademark of ADC Therapeutics SA.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 including statements regarding the potential of ZYNLONTA^® as a single-agent treatment for patients with r/r MZL, including high-risk POD24 patients, the reproducibility and durability of any favorable results initially seen in patients dosed to date, the Company's ability to enroll additional patients in the trial and expand to additional sites, the Company's research, development and regulatory plans, including the timing and results of clinical trials and the timing and outcome of regulatory submissions, and the Company's potential publication and compendia strategy. In some cases you can identify forward-looking statements by terminology such as "may", "will", "should", "would", "expect", "intend", "plan", "anticipate", "believe", "estimate", "predict", "potential", "seem", "seek", "future", "continue", or "appear" or the negative of these terms or similar expressions, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Factors that may cause such differences include, but are not limited to: future safety and efficacy results of the Phase 2  IIT in MZL and any regulatory or compendia pathways; the success of the Company's strategic restructuring plan; changes in estimated costs associated with the restructuring plan including the workforce reduction and planned closure of the UK facility; the expected cash runway into 2028 which assumes use of minimum liquidity amount required to be maintained under its loan agreement covenants; whether future LOTIS-7 clinical trial results will be consistent with or different from the LOTIS-7 data presented at EHA and ICML and future compendia and regulatory strategy and opportunity; the timing of the PFS events for LOTIS-5 and the results of the trial and full FDA approval; the Company's ability to grow ZYNLONTA^® revenue in the United States and potential peak revenue; the ability of our partners to commercialize ZYNLONTA^® in foreign markets, the timing and amount of future revenue and payments to us from such partnerships and their ability to obtain regulatory approval for ZYNLONTA^® in foreign jurisdictions; the timing and results of the Company's or its partners' research and development projects or clinical trials including LOTIS 5 and 7, as well as early pre-clinical research for our exatecan-based ADC targeting PSMA; the timing and results of investigator-initiated trials including those studying  FL and MZL and the potential regulatory and/or compendia strategy and the future opportunity; the timing and outcome of regulatory submissions for the Company's products or product candidates; actions by the FDA or foreign regulatory authorities; projected revenue and expenses; the Company's indebtedness, including Healthcare Royalty Management and Blue Owl and Oaktree facilities, and the restrictions imposed on the Company's activities by such indebtedness, the ability to comply with the terms of the various agreements and repay such indebtedness and the significant cash required to service such indebtedness; and the Company's ability to obtain financial and other resources for its research, development, clinical, and commercial activities. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K and in the Company's other periodic and current reports and filings with the U.S. Securities and Exchange Commission. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially different from any future results, performance, achievements or prospects expressed in or implied by such forward-looking statements. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this document.

CONTACT:

Investors and Media
Nicole Riley
ADC Therapeutics
Nicole.Riley@adctherapeutics.com
+1 862-926-9040

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SOURCE ADC Therapeutics SA

FAQ

What were the key efficacy results for ZYNLONTA in the Phase 2 trial for r/r MZL?

ZYNLONTA achieved an 84.6% overall response rate and 69.2% complete response rate, with 92.9% progression-free survival at 12 months

How long did the complete responses last in the ADCT ZYNLONTA trial?

17 out of 18 patients maintained their complete response, with the longest duration being 27 months from the start of treatment

What were the main side effects observed in the ZYNLONTA MZL trial?

Most adverse events were grade 1-2, with some grade 3-4 events including neutropenia, RSV lung infection, and hyponatremia. One patient discontinued due to cholestatic hepatitis

How many patients were enrolled in the ZYNLONTA Phase 2 MZL trial?

27 adult patients were enrolled with 26 being evaluable for response, and the trial is expanding to enroll up to 50 patients

What are ADC Therapeutics' plans for ZYNLONTA in MZL based on these results?

The company plans to pursue regulatory pathways and compendia in parallel once sufficient data are available, assuming continued positive results