ADC Therapeutics Completes Enrollment in LOTIS-7, Advancing ZYNLONTA-Glofitamab Combination in DLBCL

DC Therapeutics SA announced today the completion of enrollment in LOTIS-7, a phase 1b open-label trial evaluating its CD19-directed antibody-drug conjugate (ADC) loncastuximab tesirine-lpyl (Zynlonta) in combination with the bispecific antibody glofitamab (COLUMVI) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).¹ The milestone positions the combination as one of several next-generation ADC-bispecific pairings advancing within a broader wave of multifunctional biologic platforms reshaping treatment across oncology, where combination strategies are increasingly seen as a path to deeper, more durable responses.

How many patients were enrolled in the LOTIS-7 trial?

Enrollment is now complete with 100 r/r DLBCL patients dosed at the selected 150 µg/kg dose of Zynlonta plus glofitamab.¹ Patients were enrolled across 30 sites globally, with 70% in the US and 30% in the EU. The population reflects a heavily pretreated group, with 46% relapsed and 54% primary refractory disease, and a median age of 66 years — baseline characteristics consistent with other bispecific combination studies in this therapeutic space.¹

LOTIS-7 is a global, multicenter, multi-arm phase 1b study with two parts: dose escalation (Part 1) and dose expansion (part 2). The trial design includes three dosing arms — Zynlonta plus polatuzumab vedotin, Zynlonta plus glofitamab, and Zynlonta plus mosunetuzumab — though today's enrollment completion applies specifically to the glofitamab combination arm in 2L+ large B-cell lymphoma.¹ The study is registered at ClinicalTrials.gov under NCT04970901.²

What has LOTIS-7 shown so far?

Previously reported interim data from LOTIS-7 demonstrated substantial clinical activity. "We are excited by the previously reported data from this study which demonstrated an 89.8% ORR and 77.6% CR and a manageable safety profile across the 49 efficacy-evaluable patients with a minimum of 6 months of follow-up," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "We continue to believe this Zynlonta combination has the potential to be the best-in-class bispecific antibody-based combination in 2L+ DLBCL. With enrollment now complete, we look forward to sharing more comprehensive results from LOTIS-7 later this year."¹

Primary endpoints for the trial include safety and tolerability; secondary endpoints include overall response rate, duration of response, complete response, relapse-free survival, progression-free survival, overall survival, pharmacokinetics, and immunogenicity.¹ Given the mechanism of action — CD19/CD20 B-cell depletion paired with PBD payload-driven cytotoxicity — the study protocol strongly recommends anti-infective prophylaxis, intravenous immunoglobulin support for patients with B-cell loss, and vaccination.¹

Why does an ADC-bispecific combination matter in DLBCL?

DLBCL remains a difficult-to-treat malignancy in the third-line-plus setting, where patients who progress on or are ineligible for CAR-T therapy have limited options. Zynlonta, a CD19-directed ADC, already holds accelerated FDA approval and conditional EMA approval as monotherapy in this setting based on overall response rate.³ Glofitamab, a CD3xCD20 bispecific T-cell engager, brings an orthogonal immune-engaging mechanism, and pairing the two is designed to drive deeper, more durable remissions than either agent alone.

This LOTIS-7 milestone follows closely on the heels of ADC Therapeutics' LOTIS-5 Phase 3 confirmatory results reported earlier this month, in which Zynlonta plus rituximab met its primary endpoint of progression-free survival (HR=0.73; p=0.008) versus standard R-GemOx chemotherapy in 2L+ DLBCL, with no detrimental effect on overall survival.⁴ The two trials reflect ADC Therapeutics' broader strategy of pairing Zynlonta with both established (rituximab) and novel (bispecific) antibody backbones across treatment lines.

What's next for the Zynlonta-glofitamab combination?

ADC Therapeutics plans to share full data from LOTIS-7 at a medical meeting and submit results for publication by the end of 2026.¹ The company also intends to assess potential regulatory and compendia pathways for the combination, which could position Zynlonta plus glofitamab for label expansion beyond its current monotherapy indication.¹ With full data anticipated in Q4 2026, the readout will be closely watched as a test of whether ADC-bispecific combinations can outperform existing salvage regimens in heavily pretreated DLBCL.

References

1. ADC Therapeutics Announces Completion of Enrollment in LOTIS-7 Phase 1b ZYNLONTA® Combination Trial. (2026 Jun 30). PR Newswire. https://www.prnewswire.com/news-releases/adc-therapeutics-announces-completion-of-enrollment-in-lotis-7-phase-1b-zynlonta-combination-trial-302813948.html
2. A Study of ADCT-402 (Loncastuximab Tesirine) in Combination With Other Anticancer Agents (LOTIS-7). ClinicalTrials.gov. NCT04970901. https://clinicaltrials.gov/study/NCT04970901
3. FDA grants accelerated approval to loncastuximab tesirine-lpyl for large B-cell lymphoma. (2021 Apr 23). U.S. Food and Drug Administration. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-loncastuximab-tesirine-lpyl-large-b-cell-lymphoma
4. ADC Therapeutics Announces Results From LOTIS-5 Phase 3 Confirmatory Clinical Trial of ZYNLONTA® in Combination with Rituximab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. (2026 Jun 3). PR Newswire. https://ir.adctherapeutics.com/2026-06-03-ADC-Therapeutics-Announces-Results-From-LOTIS-5-Phase-3-Confirmatory-Clinical-Trial-of-ZYNLONTA-R-in-Combination-with-Rituximab-in-Relapsed-or-Refractory-Diffuse-Large-B-Cell-Lymphoma
5. Caimi PF, et al. (2021 Jun). Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. https://pubmed.ncbi.nlm.nih.gov/33989558/