ADC Therapeutics has announced the publication of Phase 2 clinical trial data in The Lancet Haematology, showcasing the efficacy of ZYNLONTA® (loncastuximab tesirine-lpyl) in combination with rituximab for relapsed or refractory (r/r) follicular lymphoma (FL). The investigator-initiated trial demonstrated a 97% overall response rate and a 77% complete response rate, offering a promising treatment option for patients with high-risk disease.
ZYNLONTA® Plus Rituximab in Follicular Lymphoma
The Phase 2 trial, conducted at the Sylvester Comprehensive Cancer Center, included patients with r/r FL who had received at least one prior line of systemic therapy and presented with high-disease burden or POD24 (progression of disease within 24 months). The primary endpoint was complete response rate (CR) by week 12, assessed via PET/CT based on Lugano 2014 criteria. The study enrolled 39 patients, with 35 evaluated for efficacy.
The patient cohort had a median age of 68 years, with most having received one prior line of therapy (67%). The most common first-line therapies were R-CHOP (56%) and bendamustine with rituximab (26%).
Key findings from the publication include:
- 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 (43.6%), increased alkaline phosphatase (41%), neutropenia, fatigue, and increased aspartate and alanine aminotransferase (38.5%). The most common grade ≥3 TEAEs were lymphopenia (20.5%) and neutropenia (12.9%). No Grade 5 TEAEs occurred.
ZYNLONTA® Monotherapy in Marginal Zone Lymphoma
Additional data from an investigator-initiated trial evaluating ZYNLONTA® monotherapy in 23 adult r/r marginal zone lymphoma (MZL) patients were presented at the American Society of Hematology (ASH) Annual Meeting. These patients had previously been treated with at least one line of systemic therapy. The median age in this study was 65 years, and the median number of previous treatments was 2.
As of October 15, 2024, 23 patients were evaluable for response. Key results included:
- ORR of 91% (n=21) and CR rate of 70% (n=16).
- ZYNLONTA® led to CR in 7 of 11 patients (64%) with POD24 and one patient who progressed after CAR-T therapy.
- All but one CR are currently maintained, with the longest follow-up of 27 months (median duration of CR is 11.5 months).
All enrolled patients experienced adverse events, mostly grade 1 or 2. Grade 3 and 4 AEs were observed in 15 and 1 patients, respectively. Local edema was observed in 43.4% of patients. Three patients required dose reduction, and one discontinued treatment due to cholestatic hepatitis, from which the patient fully recovered.
About ZYNLONTA®
ZYNLONTA® (loncastuximab tesirine-lpyl) is a CD19-directed antibody-drug conjugate (ADC). Upon binding to CD19-expressing cells, ZYNLONTA® is internalized, releasing a pyrrolobenzodiazepine (PBD) payload that binds to the DNA minor groove, leading to cell cycle arrest and tumor cell death.
ZYNLONTA® has received accelerated approval from the U.S. FDA and conditional approval from the European Medicines Agency (EMA) for treating adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. This includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics, stated, "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."
