ADC Therapeutics (ADCT) Study result summary

Study design and patient population

• Phase III LOTIS-5 was a randomized, open-label, multicenter trial comparing ZYNLONTA (loncastuximab tesirine) plus rituximab to R-GemOx in adults with 2L+ or relapsed/refractory DLBCL ineligible for stem cell transplant, enrolling 420 patients equally across arms.

• Median age was 73 years, with 41% aged 75 or older; most had DLBCL NOS histology and baseline characteristics were generally balanced except for geographic distribution.

• Over 60% of patients were primary refractory and over 40% were refractory to last therapy.

• The primary endpoint was progression-free survival (PFS) by independent central review; key secondary endpoints included overall survival (OS), overall response rate (ORR), complete response rate (CR), duration of response, safety, and patient-reported outcomes.

• Data cutoff was February 16, 2026.

Efficacy results

• The study met its primary endpoint: PFS hazard ratio was 0.73 (p=0.008), with median PFS of 6.1–6.14 months for ZYNLONTA plus rituximab vs 4.7–4.73 months for R-GemOx.

• ORR was 58.1% vs 45.2%, and CR rate was 39.5% vs 26.7%, both favoring the test arm; median duration of CR was 16.8 vs 12.3 months.

• At 24 months, 48.5% of CRs were maintained in the test arm vs 16.7% in control; event-free rates at 18 and 24 months also favored the test arm.

• No detrimental effect on OS was observed (HR 0.96, median ~12.2 months in both arms), with OS likely impacted by earlier and higher rates of new anti-lymphoma therapy in the control arm.

• Subgroup analysis showed PFS benefit in patients under 75 years (HR=0.55), but not in those 75 or older (HR=1.07).

Safety and adverse events

• Overall treatment-emergent adverse event (TEAE) rates and Grade 3+ TEAEs were similar between arms (98.5% vs 97.5%; Grade ≥3: 74% vs 76%).

• Serious TEAEs, TEAEs leading to withdrawal (25.5% vs 9.1%), and Grade 5 events (13.2% vs 4.6%) were higher in the test arm, especially in patients aged 75 or older.

• Hematologic Grade ≥3 TEAEs were higher in the control arm, while infection, hepatotoxicity, and edema/effusion were higher in the test arm.

• Longer TEAE observation time and median treatment duration (107 vs 77 days) in the test arm contributed to higher reported events.

• Physicians are expected to mitigate infection risk in elderly patients through immune assessment and prophylaxis.