ADC Therapeutics' ZYNLONTA Trial Meets PFS Endpoint in DLBCL
ADC Therapeutics SA announced topline data from its Phase 3 LOTIS-5 trial evaluating ZYNLONTA® (loncastuximab tesirine-lpyl) in combination with rituximab for relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). The trial met its primary endpoint of progression-free survival (PFS) with statistical significance, showing a median PFS of 6.1 months for the ZYNLONTA combination versus 4.7 months for the control arm (R-GemOx). While overall survival showed no detrimental effect, the ZYNLONTA combination demonstrated higher overall response rates (58.1% vs. 45.2%) and complete response rates (39.5% vs. 26.7%). The company noted higher rates of serious adverse events and Grade 5 events in the ZYNLONTA arm, particularly in older patients, and plans to proceed with regulatory discussions, aiming for an sBLA submission in Q4 2026. ADC Therapeutics is also evaluating value-maximizing alternatives.
Key Highlights
- ADC Therapeutics' LOTIS-5 Phase 3 trial met primary endpoint for ZYNLONTA + rituximab in r/r DLBCL.
- Median Progression-Free Survival (PFS) was 6.1 months for ZYNLONTA + rituximab vs. 4.7 months for R-GemOx (HR=0.73, p=0.008).
- Overall Response Rate (ORR) was 58.1% for ZYNLONTA + rituximab vs. 45.2% for R-GemOx.
- Complete Response (CR) rate was 39.5% for ZYNLONTA + rituximab vs. 26.7% for R-GemOx.
- Serious Adverse Events (SAEs) were higher in the ZYNLONTA + rituximab arm (49.0% vs. 34.5%).
- Grade 5 TEAEs were higher in the ZYNLONTA + rituximab arm (13.2% vs. 4.6%), mostly in patients >= 75 years old.
- Company plans pre-sBLA meeting with FDA in August and sBLA submission in Q4 2026.
Price Impact
More from ADCT