ADC Therapeutics (ADCT) Study Update summary

Strategic Overview and Study Rationale

• Zynlonta is positioned as a single-agent therapy in third-line plus DLBCL, with expansion plans into earlier lines and indolent lymphomas through combinations.

• LOTIS-7 is a Phase 1b trial evaluating Zynlonta with glofitamab, a bispecific antibody, for relapsed/refractory large B-cell lymphoma, including DLBCL, FL, and MZL.

• The combination targets two B-cell antigens, offering complementary mechanisms and potential additive or synergistic efficacy.

• Dosing Zynlonta before glofitamab is hypothesized to debulk tumors and reduce CRS rates.

• Primary endpoints are safety, tolerability, and recommended dose; secondary endpoints include ORR, CRR, DOR, PFS, and OS.

Study Design and Patient Population

• Dose escalation is complete; dose expansion is ongoing at 120 and 150 mcg/kg Zynlonta plus glofitamab at its approved dose, targeting ~100 patients.

• 49 efficacy-evaluable patients with r/r LBCL, median age 70 (range 26–85), median prior lines of therapy 1 (range 1–5), 59% male, 51% with high LDH.

• 16% had prior CAR-T therapy, 6% prior SCT, and 16% had double/triple hit lymphoma; both primary refractory and relapsed patients included.

• The study aims for a balanced population representative of real-world second-line plus DLBCL.

• 51% were refractory to last prior therapy; 61% had only one prior line.

Efficacy Results

• ORR was 89.8% (44/49), with a CR rate of 77.6% (38/49); 33/38 CRs were ongoing at data cutoff.

• Median time to response was 42 days; 14 patients converted from SD/PR to CR over time.

• In relapsed patients, ORR was 100% and CR rate 91.6%; in primary refractory, ORR was 80% and CR rate 64%.

• Six of eight patients with prior CAR-T achieved CR.

• 33 of 38 patients achieving CR remained in CR at data cutoff; only two progressed.