ADC Therapeutics Announces Presentation of LOTIS-7 Clinical Trial Data at the European Hematology Association 2025 Congress (EHA2025) and the 18th International Conference on Malignant Lymphoma (ICML)
ZYNLONTA® plus glofitamab (COLUMVI®) demonstrated ORR of 95.5% and CR of 90.9%, among 22 evaluable patients with relapsed/refractory DLBCL
Safety and tolerability data were consistent with the known profiles of each agent
Updated data to be shared during poster presentation at EHA2025 on Saturday, June 14 at 12:30 p.m. ET and oral presentation at ICML on Friday, June 20 at 9:00 a.m. ET
LAUSANNE, Switzerland, May 14, 2025 /PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced 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). Updated results will be shared at the European Hematology Association 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 EHA2025.
ADC Therapeutics logo (PRNewsfoto/ADC Therapeutics SA)
"We are excited to present the latest LOTIS-7 data from a larger subset of patients with longer follow-up at EHA 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 EHA2025.
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 EHA2025 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.
About ADC Therapeutics ADC Therapeutics (NYSE: ADCT) is a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs). The Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.
ADC Therapeutics' CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing development.
ADC Therapeutics is based in Lausanne (Biopôle), Switzerland and has operations in London and New Jersey. For more information, please visit https://adctherapeutics.com/ and follow the Company on LinkedIn.
ZYNLONTA® is a registered trademark of ADC Therapeutics SA.
Forward-Looking Statements This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. In some cases you can identify forward-looking statements by terminology such as "may", "will", "should", "would", "expect", "intend", "plan", "anticipate", "believe", "estimate", "predict", "potential", "seem", "seek", "future", "continue", or "appear" or the negative of these terms or similar expressions, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Factors that may cause such differences include, but are not limited to: the expected cash runway into mid-2026 the Company's ability to grow ZYNLONTA® revenue in the United States; the ability of our partners to commercialize ZYNLONTA® in foreign markets, the timing and amount of future revenue and payments to us from such partnerships and their ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions; the timing and results of the Company's or its partners' research and development projects or clinical trials including LOTIS 5 and 7, ADCT 602, as well as early research in certain solid tumors with different targets, linkers and payloads; the timing and results of investigator-initiated trials including those studying FL and MZL and the potential regulatory and/or compendia strategy and the future opportunity; the timing and outcome of regulatory submissions for the Company's products or product candidates; actions by the FDA or foreign regulatory authorities; projected revenue and expenses; the Company's indebtedness, including Healthcare Royalty Management and Blue Owl and Oaktree facilities, and the restrictions imposed on the Company's activities by such indebtedness, the ability to comply with the terms of the various agreements and repay such indebtedness and the significant cash required to service such indebtedness; and the Company's ability to obtain financial and other resources for its research, development, clinical, and commercial activities. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K and in the Company's other periodic and current reports and filings with the U.S. Securities and Exchange Commission. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially different from any future results, performance, achievements or prospects expressed in or implied by such forward-looking statements. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this document.
