ADC Therapeutics' Zynlonta-glofitamab combo posts 89.8% response rate in LOTIS-7
Interim data from a lymphoma combination trial show an 89.8% overall response rate in 49 patients, even as the registry trims target enrollment and pushes the completion date to 2027.
Executive Summary
- A Phase 1 combination trial pairing ADC Therapeutics' antibody-drug conjugate with a bispecific antibody has posted a response rate above 89% in relapsed or refractory B-cell non-Hodgkin lymphoma patients, a population that has already exhausted at least two prior lines of therapy.
- Alongside that disclosure, the trial's registered enrollment target was trimmed and its primary completion date pushed out roughly five months, changes that reflect the study narrowing toward its most promising arm rather than a program in distress.
- The combination enters a CD19-targeted field crowded with CAR-T therapies and bispecific antibodies already approved or in late-stage testing, where an antibody-drug-conjugate-based combination is one of relatively few entrants using that mechanism.
- ADC Therapeutics has said it plans to present the full LOTIS-7 dataset at a medical meeting and in a publication by the end of 2026, which would let the response rate be judged for durability rather than as a single-timepoint readout.
The disclosure
ADC Therapeutics S.A. reported that its combination of loncastuximab tesirine (Zynlonta) and glofitamab produced an 89.8% overall response rate and a 77.6% complete response rate in 49 efficacy-evaluable patients enrolled in the LOTIS-7 trial (NCT04970901). The trial studies loncastuximab tesirine, an antibody-drug conjugate directed at CD19 and already carrying accelerated FDA approval for relapsed or refractory large B-cell lymphoma after two or more prior lines of therapy, in combination with several partner agents in patients who have exhausted standard options. The disclosed cohort completed enrollment at the 150 microgram/kg selected dose, with the sponsor describing a manageable safety profile. AA Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)Jul 17, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The registry moves
The same update that carried the efficacy figures also changed three registered facts about the trial: enrollment moved from 200 to 154, status shifted from Recruiting to Active, not recruiting, and the primary completion date moved from October 30, 2026 to March 31, 2027. The trial has adjusted its primary completion date three times since 2025, most recently by five months in September 2025 and again in this update. Enrollment closing alongside a shift to Active, not recruiting is the expected pattern once a Phase 1b dose-expansion cohort finishes accrual, not an operational warning sign; the operational model flags enrollment changes at 20% or more, and this trial's enrollment move falls within routine range for its design. NCT04970901A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)NCT04970901
The design
LOTIS-7 is an open-label, non-randomized, six-arm Phase 1 study testing loncastuximab tesirine against multiple combination partners, including polatuzumab vedotin, glofitamab, and mosunetuzumab, in patients with relapsed or refractory large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma. Its primary endpoints track dose-limiting toxicities, treatment-emergent adverse events, and safety-laboratory changes rather than efficacy alone, consistent with a dose-escalation and dose-expansion design. The trial is not registrational. NCT04970901A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)NCT04970901
The competitive frame
The CD19-targeted field in B-cell non-Hodgkin lymphoma is crowded: 24 active industry trials target CD19 in this indication, and Phase 1 programs targeting CD19 in this setting have failed at a 64% rate historically, with seven distinct sponsors recording failures. Approved CD19-directed options already include CAR-T therapies such as Gilead Sciences' axicabtagene ciloleucel and bispecific antibodies such as Genmab's epcoritamab, both tested in Phase 3 programs in the same target-indication space. Antibody-drug conjugates remain a minority modality in this field, with seven trials on record using that approach against CD19 in B-cell non-Hodgkin lymphoma, compared with the CAR-T and bispecific programs that dominate late-stage development. Against that backdrop, a combination pairing an approved antibody-drug conjugate with a bispecific antibody would need to show that its response rate holds up with longer follow-up and translates into durable remissions to distinguish itself from monotherapy options already reaching patients. [landscape]
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.