On June 12, 2025 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported updated data from the LOTIS-7 Phase 1b open-label clinical trial evaluating the safety and efficacy of ZYNLONTA in combination with the bispecific antibody glofitamab (COLUMVI) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress (EHA2025) in Milan, Italy (Press release, ADC Therapeutics, JUN 12, 2025, View Source [SID1234653863]). The Company will host a conference call and webcast featuring LOTIS-7 trial principal investigator and EHA (Free EHA Whitepaper) presenting author, Juan Alderuccio, MD, Clinical Site Disease Group Leader, Lymphoma Section, at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine today at 8:00 a.m. ET to discuss the results. To access the conference call, please register here.
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"The data seen in this study with the combination of ZYNLONTA and glofitamab has shown a manageable safety profile along with strong efficacy data from patients with relapsed or refractory DLBCL, with complete responses observed regardless of prior therapy, including CAR-T," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "The combination of these two anti-cancer agents holds significant promise for advancing the treatment landscape and addressing unmet need in patients with these hard-to-treat lymphomas."
The presentation highlights updated data as of April 14, 2025, in which r/r LBCL patients received dose levels of 120 µg/kg or 150 µg/kg of ZYNLONTA plus the bispecific antibody glofitamab, with 41 patients evaluable for safety and 30 patients evaluable for efficacy.
Key highlights of the LOTIS-7 data presentation are as follows:
Best overall response data among the 30 efficacy evaluable patients shows overall response rate (ORR) of 93.3% (28/30 pts) as assessed by Lugano Criteria
Complete response (CR) rate of 86.7% (26/30 pts)
Of these, 25/26 patients achieving CR remain in CR as of the data cut-off
Median time to CR in 120 µg/kg = 80 days
Median time to CR in 150 µg/kg = 42 days
12 patients converted from stable disease (SD) or partial response (PR) to CR over time (1 and 11 pts respectively)
Of the 6 patients previously treated with CAR-T and undergoing response assessment, 5 achieved a CR
Among the 41 safety evaluable patients, the combination was generally well tolerated with a manageable safety profile and no DLTs across dose levels
Grade 3 or higher treatment emergent adverse events (TEAEs) observed in > 5% of patients included neutropenia (24.4%), anemia (9.8%), AST increased (7.3%), GGT increased (7.3%), and thrombocytopenia (7.3%)
In the 150 µg/kg dose, cytokine release syndrome (CRS) (23.8%), all of which were Grade 1, and immune effector cell-associated neurotoxicity syndrome (ICANS) (4.8%), with one case of Grade 2, were observed
In the 120 µg/kg dose, CRS all grades (55%), all of which were Grade 1/2 except one case of Grade 3, and ICANS (10%), with one case of Grade 1 and one case of Grade 2, were observed
TEAEs leading to discontinuation included 3 each for ZYNLONTA and glofitamab
There were no Grade 5 TEAEs observed
"We believe these new data are differentiating and further reinforce the potential of ZYNLONTA plus the bispecific glofitamab to improve outcomes for DLBCL patients who need it most," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "This early safety and efficacy data support the ongoing expansion of this study to 100 patients at the 150 µg/kg dose of ZYNLONTA plus glofitamab. We look forward to discussing the results with Dr. Alderuccio during our conference call today in addition to the presentation of the data set across two key conferences."
This data will be shared at EHA (Free EHA Whitepaper)2025 during a poster presentation on June 14 at 6:30 p.m. CEST and also as an oral encore presentation at the 18th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland on Friday, June 20 at 9:00 a.m. ET. The Company plans to share additional data before the end of 2025.
Conference Call Information
To access the conference call, please register here. The participant toll-free dial-in number is 1-800-836-8184 for North America and Canada. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under "Events and Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.
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.