On December 3, 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). The updated data is based on investigator assessment and reflects the 49 efficacy-evaluable patients with a minimum of 6 months of follow-up from treatment initiation.
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"We’re excited that these data continue to demonstrate a manageable safety profile and strong efficacy including deep and durable responses in 2L+ r/r DLBCL patients treated with ZYNLONTA plus glofitamab," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "We are well on the way to completing enrollment of approximately 100 patients at the selected dose and plan to share full results at a medical congress and through a publication by the end of next year."
As of the November 17, 2025 cutoff date, a total of 49 patients were efficacy evaluable with a minimum of 6 months of follow-up from treatment initiation. Key highlights of the data are as follows:
Best overall response rate (ORR) was 89.8% (44/49 patients) as assessed by Lugano criteria
Complete response (CR) rate was 77.6% (38/49 patients)
Of these, 33/38 patients achieving CR remain in CR as of the data cutoff; the 5 patients who did not remain in CR included 2 patients with progressive disease, 2 patients with Grade 5 AEs which occurred during CR, and one censored patient
Strong efficacy in both the relapsed and primary refractory populations across both dose levels
In the 24 relapsed patients ORR was 100% and CR rate was 91.7%
In the 25 primary refractory patients ORR was 80% and CR rate was 64%
14 patients converted from stable disease (SD) or partial response (PR) to CR over time (1 and 13 patients respectively)
Of the 8 patients previously treated with CAR-T, 6 achieved a CR
The combination was generally well tolerated with a manageable safety profile
Grade 3 or higher treatment emergent adverse events (TEAEs) observed in > 5% of patients included neutropenia (32.7%), GGT increased (16.3%), anemia (10.2%), WBC decreased (8.2%), generalized oedema (8.2%), ALT increased (8.2%), AST increased (6.1%), and thrombocytopenia (6.1%)
Grade 5 AEs occurred in 2 (4.1%) patients; one was treatment-related per the investigator
Cytokine release syndrome (CRS) of all grades across dose levels was 36.7%
CRS all grades was 25.0% at the selected 150 µg/kg dose and 52.4% at the 120 µg/kg dose, with all but one low Grade
Immune effector cell-associated neurotoxicity syndrome (ICANS) was 4.1% across dose levels, with only Grade 1/2
"We believe these updated data further strengthen the evidence supporting the differentiated profile of the combination of ZYNLONTA and glofitamab, which has the potential to be the best-in-class bispecific antibody-based combination in 2L+ DLBCL," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "Taken together with the LOTIS-5 trial, for which top-line results are anticipated in the first half of 2026, we believe ZYNLONTA-based combinations offer complementary approaches with the potential to improve outcomes for 2L+ DLBCL patients."
Enrollment in the LOTIS-7 clinical trial is ongoing, with complete enrollment of approximately 100 patients at the selected 150 µg/kg dose expected during the first half of 2026. The Company plans to share full data at a medical meeting and submit for publication by the end of 2026. In addition, the Company plans to assess regulatory and compendia strategies.
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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.
(Press release, ADC Therapeutics, DEC 3, 2025, View Source [SID1234661118])