On May 14, 2025 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported data presentations from the LOTIS-7 Phase 1b clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) in combination with glofitamab in patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) (Press release, ADC Therapeutics, MAY 14, 2025, View Source [SID1234653097]). Updated results will be shared at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress (EHA2025) taking place in Milan, Italy with an oral encore presentation at the 18th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. Updated LOTIS-5 safety run-in data evaluating the combination of ZYNLONTA plus rituximab (Lonca-R) will also be featured at EHA (Free EHA Whitepaper)2025.

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"We are excited to present the latest LOTIS-7 data from a larger subset of patients with longer follow-up at EHA (Free EHA Whitepaper) and ICML," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "The robust efficacy and manageable safety seen to date with the combination of ZYNLONTA and glofitamab, two potent anti-cancer agents with different mechanisms of action, reinforce the potential for this regimen to change the treatment paradigm for patients with aggressive lymphoma."

The LOTIS-7 abstract provides data as of the January 17, 2025, cutoff, in which 31 patients received ≥1 ZYNLONTA dose and were safety evaluable, with 22 patients efficacy evaluable. Four of these patients (2 each at 120µg/kg and 150 µg/kg) converted to complete response (CR) within 3 weeks after the data cutoff and are included as CRs. Updated data will be presented during EHA (Free EHA Whitepaper)2025.

Key highlights in the LOTIS-7 abstract are as follows:

In the efficacy evaluable population, overall response rate (ORR) was 95.5% (21/22), complete response (CR) rate was 90.9% (20/22), and median duration of response (DOR) was not reached.
Among 31 patients treated, the combination demonstrated a manageable safety profile.
Adverse events were consistent with known profiles of the individual agents, with neutropenia (32.3%) being the most common Grade ≥3 treatment-emergent adverse event (TEAEs). Grades 3/4 TEAEs of interest included generalized edema, pericardial effusion, photosensitivity reaction, rash, sepsis and pneumonia (each 3.2%). Grade 1/2 AE of CRS (29.0%/9.7%) and ICANS (0%/6.5%) were observed with no Grade ≥3 at the time of data cut off.
Details of the EHA (Free EHA Whitepaper)2025 poster presentations are as follows:
Title: Initial Results From LOTIS-7: A Phase 1b Study of Loncastuximab Tesirine Plus
Glofitamab in Patients With Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Session: Poster Session 2
Session Date and Time: Saturday, June 14; 12:30-1:30 p.m. ET / 18:30 -19:30 CEST
Location: Poster Hall, Allianz MiCo, Milano Convention Centre
Presenting Author: Juan Pablo Alderuccio, MD, Associate Professor of Medicine and Hematologist at Sylvester Comprehensive Cancer Center, University of Miami
Abstract: PS1911

Title: Updated Safety Run-In Results From LOTIS-5: A Phase 3, Randomized Trial of Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Patients With R/R DLBCL/HGBL
Session: Poster Session 2
Session Date and Time: Saturday, June 14; 12:30-1:30 p.m. ET / 18:30 -19:30 CEST
Location: Poster Hall, Allianz MiCo, Milano Convention Centre
Presenting Author: Carmelo Carlo-Stella, MD, PhD, section chief of Lymphoid Malignancies and Cancer Therapeutics at Humanitas Clinical and Research Center (IRCCS)
Abstract: PS1957

Details of the ICML oral encore presentation are as follows:
Title: Initial Results From LOTIS-7: A Phase 1b Study of Loncastuximab Tesirine Plus Glofitamab in Patients With Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Session: 13 – Aggressive B-Cell Lymphomas
Session Date and Time: Friday, June 20; 8:00 a.m.-9:30 a.m. ET / 14:00-15:30 CEST
Location: Room A, broadcast in Cinema Corso, Lugano Convention Centre, Palazzo dei Congressi
Presenting Author: Juan Pablo Alderuccio, MD, Associate Professor of Medicine and Hematologist at Sylvester Comprehensive Cancer Center, University of Miami
Abstract: 078

Additionally, a poster entitled, "Updated analysis of a phase 2 multicenter study of the loncastuximab in relapsed/refractory marginal zone lymphoma demonstrates high rate of complete responses" will be presented at ICML. This single-arm, open-label investigator-initiated study is being conducted at the Sylvester Comprehensive Cancer Center at University of Miami and City of Hope, and led by Izidore Lossos, MD, Professor, Director, Lymphoma Program at the Sylvester Comprehensive Cancer Center, University of Miami.

About LOTIS-7
LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). The three dosing arms include ZYNLONTA plus polatuzumab vedotin, ZYNLONTA plus glofitamab, and ZYNLONTA plus mosunetuzumab T-cell-engaging bispecific monoclonal antibodies (BsAbs). Enrollment in LOTIS-7 includes Part 1 of the study with a 3+3 dose escalation in 3L/3L+ heavily pre-treated patients with ZYNLONTA doses starting at 90 µg/kg and then proceeding to 120 µg/kg and 150 µg/kg. Part 2 includes dose expansion in 2L/2L+ large B-cell lymphoma in the ZYNLONTA plus glofitamab arm at dose levels determined from Part 1 (120 µg/kg and 150 µg/kg of ZYNLONTA plus the approved dosing of glofitamab). Primary endpoints of the study include safety and tolerability. Secondary efficacy endpoints include ORR, DOR, CRR, PFS, RFS, and OS as well as pharmacokinetics and immunogenicity.

For more information about the LOTIS-7 trial, visit clinicaltrials.gov (NCT04970901).

About ZYNLONTA
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.