On December 9, 2024 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported updated data from the investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) in combination with rituximab to treat relapsed or refractory (r/r) follicular lymphoma (FL) were published in the December issue of The Lancet Haematology, following an oral presentation of the data at the recent 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, ADC Therapeutics, DEC 9, 2024, View Source [SID1234648941]).
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"We are excited by the publication of these results in The Lancet Haematology demonstrating ZYNLONTA’s robust clinical activity in follicular lymphoma, particularly in patients classified as high-risk POD24 and those with high tumor burden where there remains significant unmet need," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "In addition, encouraging data from another investigator-initiated trial of ZYNLONTA as a single agent to treat marginal zone lymphoma were also presented at ASH (Free ASH Whitepaper). Collectively, we believe these data underscore ZYNLONTA’s promise for patients with indolent B-cell lymphomas and add to a growing body of evidence showing the potential of ZYNLONTA beyond diffuse large B-cell lymphoma."
ZYNLONTA in combination with rituximab to treat r/r follicular lymphoma (FL)
The investigator-initiated trial conducted at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine evaluated the combination in patients with r/r FL treated with ≥1 line of systemic therapy presenting high-disease burden as defined by GELF criteria or POD24 at enrollment. The primary endpoint of the study is complete response rate (CR) by week 12 PET/CT based on Lugano 2014 criteria. The trial enrolled 39 patients, all of which were evaluated for safety and 35 of which were evaluated for efficacy.
Patients were a median age of 68 years (range 47 to 89) and the majority received one previous line of therapy (n=26; 67%). R-CHOP was the most common first-line therapy (n=22; 56%) followed by bendamustine with rituximab (n=10; 26%), single-agent rituximab (n=6; 15%) and fludarabine, mitoxantrone and dexamethasone (n=1; 3%).
Highlights from the results published in The Lancet Haematology included:
Best overall response rate (ORR) of 97.4% (n=38) and CR rate of 76.9% (n=30)
After a median follow-up of 15.6 months, the median progression-free survival (PFS) was not reached, and the 12-month PFS was 94.6%
The most common treatment-emergent adverse events (TEAEs) were hyperglycemia (n=17; 43.6%) followed by increased alkaline phosphatase (n=16; 41%) and neutropenia, fatigue and increased aspartate aminotransferase and alanine aminotransferase (n=15; 38.5%)
The most common grade ≥3 TEAE were lymphopenia (n=8; 20.5%) followed by neutropenia (n=5; 12.9%)
No Grade 5 TEAEs occurred.
The publication titled, "Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single centre, single arm Phase 2 trial," is now available online and will be published in the December issue of The Lancet Haematology. The results were also presented during a session on indolent B-cell lymphomas at ASH (Free ASH Whitepaper) by Juan Pablo Alderuccio, MD, lead investigator and Associate Professor of Medicine and Hematologist at Sylvester. More details on the trial can be found at View Source (identifier: NCT04998669).
ZYNLONTA as a single agent to treat r/r marginal zone lymphoma (MZL)
Data from an open-label, multi-institutional investigator-initiated trial evaluating the safety and efficacy of ZYNLONTA in 23 adult r/r MZL patients, previously treated with ≥1 line of systemic therapy, were also shared as a poster presentation at ASH (Free ASH Whitepaper) by lead investigator, Izidore Lossos, MD, Professor of Medicine and Chief of the Lymphoma Section of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. The median age in this study was 65 years (range 45-82). The median number of previous treatments was 2 (range 1 to 4).
As of October 15, 2024, 23 patients were evaluable for response. Highlights from the results presented include:
ORR of 91% (n=21); 70% CR (n=16). ZYNLONTA led to CR in 7 of 11 patients (64%) with POD24 assessed for response and one patient who progressed after CAR-T.
All but 1 CR are currently maintained with the longest follow-up of 27 months from the start of treatment (median duration of CR is 11.5 months).
All of the 23 enrolled patients experienced expected adverse events (AE), most commonly grade 1 or 2. Grade 3 and 4 AEs were observed in 15 and 1 (neutropenia) patients, respectively. Local edema was observed in 10 (43.4%) patients. Three patients needed dose reduction and one patient discontinued treatment after cycle 4 because of cholestatic hepatitis. The patient clinically fully recovered with normalization in liver function test abnormalities.
More details on this ongoing Phase 2 clinical trial can be found at View Source (identifier: NCT05296070).
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.