Zynlonta (loncastuximab tesirine-lpyl) / Overland ADCT BioPharma, Tanabe Pharma, SOBI - LARVOL DELTA

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) (SOHO 2025) - P1 | "Lonca-Glofit in R/R B-NHL showed a manageable/consistent safety profile and encouraging efficacy in heavily pretreated aggressive lymphoma patients. Results suggest Lonca complements Glofit's mechanism and provides additive efficacy. Funding: ADC Therapeutics SA and Sobi; medical writing: Citrus Health Group."

Clinical • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4 • CD8 • IL6

Consolidation with Loncastuximab Tesirine for Large B-cell Lymphoma Patients in Partial Response after CART: Planned Interim Futility Analysis of a Phase II Trial (TCT-ASTCT-CIBMTR 2026) - P2 | "Median age was 74 (range, 45-84), 8 (80%) were male, 6 (60%) had received axicabtagene ciloleucel and 4 (40%) had received lisocabtagene maraleucel. Consolidation is a viable strategy to drive conversion from partial to complete response. Loncastuximab tesirine is an antibody-drug conjugate with tolerable safety profiles when used in post- CAR consolidation."

Clinical • P2 data • B Cell Lymphoma • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

Loncastuximab Tesirine in Combination with Venetoclax Is Safe and Shows Efficacy in Patients with Relapsed/Refractory Non Hodgkin Lymphoma (ASH 2024) - "Enrollment continues in a dose expansion cohort that also includes patients with r/r mantle cell lymphoma. Updated analyses with longer follow-up and expanded enrollment will be presented."

Clinical • Combination therapy • Acute Kidney Injury • Anemia • Atrial Fibrillation • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Leukopenia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Thrombocytopenia • Waldenstrom Macroglobulinemia

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) (ICML 2025) - P1 | "Lonca+Glofit in R/R B-NHL showed a manageable safety profile consistent with each drug and encouraging efficacy in heavily pretreated aggressive lymphoma pts. Lonca+Glofit induced T-cell margination, and sustained circulating CD4+ and CD8+ T-cell activation was noted. Results support that Lonca complements Glofit's mechanism and provides additive efficacy."

Clinical • IO biomarker • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4 • CD8 • IL6

Treatment and Survival Outcomes in Follicular Lymphoma Patients with POD24: A Systematic Review and Meta-Analysis. (PubMed, Blood Adv) - "Anti-CD19 antibody-drug conjugates (ADCs)/ monoclonal antibody (mAb): the ORR and CR of Loncastuximab+ rituximab and Tafasitamab+R2 (lenalidomide+rituximab) were 100%, 79.3% and 87.5%, 43.2%, respectively. Additionally, bispecific antibodies, anti-CD19 ADC/mAb, and the combination of lenalidomide with obinutuzumab or rituximab also exhibited excellent efficacy. Notably, lenalidomide plus obinutuzumab showed superior efficacy compared to R2."

Journal • Retrospective data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Limited Duration Loncastuximab Tesirine with Rituximab Induces High Complete Metabolic Response Rate in High-Risk Relapsed/Refractory Follicular Lymphoma – a Phase 2 Study (ASH 2023) - P2 | "Premedication with dexamethasone 4 mg twice daily for 3 days was required with loncastuximab...R-CHOP was most common first-line therapy (n=14; 54%) followed by bendamustine with rituximab and single-agent rituximab (n=6; 23%; each)... A limited duration program combining loncastuximab with rituximab in patients with rel/ref FL is well tolerated and highly effective with a metabolic CR rate of 86% including high-risk patients with POD24 and/or high disease burden."

P2 data • B Cell Lymphoma • Biliary Cancer • Cholangiocarcinoma • Dermatology • Diffuse Large B Cell Lymphoma • Fatigue • Follicular Lymphoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Solid Tumor • Thrombocytopenia

Deep responses following treatment with loncastuximab tesirine (WM-NET1 trial) in patients with Relapsed/Refractory including those withhigh-risk, TP53-altered Waldenström macroglobulinemia. (ASH 2025) - P2 | "Our findings from this ongoing, prospective trial demonstrate a high VGPR/CR rate of 71% inheavily pre-treated WM. Notable, is the VGPR/CR rate of 89% in high-risk patients with TP53ALT WM. Nounexpected toxicities have been seen in this trial."

Clinical • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CA6 • CXCR4 • MYD88 • TP53

A Phase 2, Open-Label Study of Loncastuximab Tesirine in Combination With Rituximab (Lonca-R) in Previously Untreated Unfi t/Frail Patients With Diffuse Large B-Cell Lymphoma (LOTIS-9) (SOHO 2022) - P2 | "Background: Rituximab in combination with chemotherapy (R [rituximab]-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) is standard fi rst-line therapy for patients with diffuse large B-cell lymphoma (DLBCL). The study opened for recruitment in April 2022. This abstract was accepted for publication only at the 2022 EHA Congress. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group."

Clinical • Combination therapy • P2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single-centre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "Loncastuximab tesirine with rituximab showed clinically meaningful activity in relapsed or refractory follicular lymphoma, and had a manageable safety profile."

Journal • P2 data • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology

Beyond R-CHOP: The rise of antibody-drug conjugates in DLBCL. (PubMed, Blood Rev) - "Recently, ADCs have expanded the DLBCL therapeutic landscape, with the approvals of CD79b-targeted polatuzumab vedotin and CD19-directed loncastuximab tesirine for R/R and even frontline disease. However, the clinical application of ADCs is accompanied by challenges, including the management of characteristic toxicities, understanding and overcoming mechanisms of resistance. This review systematically synthesizes the mechanisms of action, updated clinical evidence, toxicity profiles, and resistance mechanisms of ADCs in DLBCL, while also discusses management strategies and provides perspectives on future directions."

Journal • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22 • CD79B • TNFRSF8

Loncastuximab Tesirine in Heavily Pretreated Patients with Diffuse Large B-cell Lymphoma, Including the Post-CAR-T Setting: A Meta-Analysis (TCT-ASTCT-CIBMTR 2026) - "Loncastuximab tesirine demonstrates substantial clinical activity and a manageable safety profile in heavily pretreated patients with R/R DLBCL, including in the post-CAR-T setting. However, the modest progression-free survival indicates that durable responses might be challenging to achieve with monotherapy. 1 ."

Retrospective data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Limited Duration Loncastuximab Tesirine Induces a High Rate of Complete Responses in Patients with Relapsed/Refractory Marginal Zone Lymphoma - Report of First Planned Interim Futility Analysis of a Multicenter Phase II Study (ASH 2024) - P2 | "Premedication with dexamethasone 4 mg twice daily for 3 days and prophylaxis with spironolactone 100 mg (to prevent fluid overload) was required...At the time of study design, the best reported CR rate in r/r MZL was 16% achieved with umbralisib, that we used as P0 assumption under the null hypothesis...Across all lines of treatment, the most common treatments were R-chemotherapy (n=18), targeted/immuno-modulatory agents (n=7) and single-agent rituximab (n=7); 1 patient had CAR-T...The patient clinically fully recovered with normalization in LFTs abnormalities. Conclusion : Lonca is demonstrating clinically meaningful activity with robust CR rate in r/r MZL patients in our ongoing phase 2 study."

Clinical • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab Tesirine with Rituximab Induces Robust and Durable Complete Metabolic Responses in High-Risk Relapsed/Refractory Follicular Lymphoma (ASH 2024) - P2 | "R-CHOP was the most common first-line therapy (56.5%), followed by bendamustine with rituximab (25.6%), single-agent rituximab (15.3%), and fludarabine, mitoxantrone and dexamethasone (2.6%). Conclusion : Loncastuximab with rituximab demonstrates dramatic activity with robust CMR and 12-month PFS of 94.2% in high-risk r/r FL. Our study supports this combination as a new treatment option in FL, and a multicenter expansion cohort is ongoing."

Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Fatigue • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mood Disorders • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

A Phase II Trial of Loncastuximab Tesirine in Patients with Previously Treated Waldenström Macroglobulinemia (ASH 2024) - "This prospective phase II clinical trial was designed to evaluate the use of loncastuximab tesirine, a CD19 antibody drug conjugate, in patients with WM previously treated with at least two lines of therapy, including rituximab and a BTK inhibitor. This treatment has a manageable side effect profile with skin toxicity, asymptomatic GGT elevation, and transient cytopenias that have not led to treatment discontinuation. Accrual will continue to enroll 36 total patients."

Clinical • IO biomarker • P2 data • Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CXCR4 • MYD88 • TP53

Deep Learning-Based Body Composition Analysis for Outcome Prediction in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Insights From the LOTIS-2 Trial. (PubMed, JCO Clin Cancer Inform) - P2 | "The pretreatment SM*/VF* body composition index shows promise as a biomarker for patients with rel/ref DLBCL undergoing treatment with loncastuximab tesirine. The proposed deep learning-based approach for body composition analysis demonstrated comparable performance to the manual process, presenting a more cost-effective alternative to conventional methods."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study. (PubMed, Blood Adv) - No abstract available

Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Metabolic Tumor Volume Predicts Outcomes in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated with Loncastuximab Tesirine in the Lotis-2 Trial (ASH 2022) - P2 | "In the present analysis we demonstrated the predictive impact of PET/CT data in rel/ref DLBCL retaining its risk-stratification power as continuous and categorical variables. MTV is an imaging biomarker extracted from routine PET/CT scans and enables individualized treatment selection identifying those patients that will benefit the most from loncastuximab tesirine."

Biomarker • Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase II Study of Loncastuximab Tesirine as Consolidation Strategy in Patients With LBCL in PR After CAR T-cell Therapy (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jan 2026 ➔ Jan 2030 | Trial primary completion date: Jan 2026 ➔ Jan 2030

Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Investigator-initiated trials (IITs) of ZYNLONTA in indolent lymphomas ongoing (PRNewswire) - "Initial data from the Phase 2 clinical trial evaluating ZYNLONTA in combination with rituximab to treat relapsed or refractory (r/r) follicular lymphoma (FL) and the Phase 2, single-arm, open-label, multicenter trial of ZYNLONTA to treat r/r marginal zone lymphoma (MZL) led by the Sylvester Comprehensive Cancer Center at University of Miami have shown promising efficacy and manageable safety results. The Company anticipates publication of both data sets as early as the end of 2026."

P2 data • Trial status • Follicular Lymphoma • Marginal Zone Lymphoma

The Company expects to provide topline data in 2Q 2026 from the LOTIS-5 Phase 3 confirmatory trial of ZYNLONTA in combination with rituximab in patients with 2L+ DLBCL once the pre-specified number of approximately 262 progression-free survival (PFS) events is reached and data are available (PRNewswire) - "Publication of the full results is anticipated by the end of 2026. Assuming positive results, a supplemental Biologics License Application (sBLA) submission to the U.S. FDA will follow, with potential compendia inclusion in the first half of 2027 and confirmatory approval in 2L+ DLBCL in mid-2027."

FDA approval • FDA filing • P3 data: top line • Diffuse Large B Cell Lymphoma

ADC Therapeutics Provides…Recent Corporate Updates (PRNewswire) - "Enrollment in the LOTIS-7 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 through publication by the end of 2026."

Enrollment status • P1 data • Diffuse Large B Cell Lymphoma

Chemical evolution of antibody-drug conjugates focused on linker design and conjugation strategies in hematology. (PubMed, Semin Hematol) - "Case studies of FDA-approved ADCs, including brentuximab vedotin, polatuzumab vedotin, inotuzumab ozogamicin, and loncastuximab tesirine, demonstrate how these innovations translate into therapeutic benefit. Nonetheless, challenges such as antigen heterogeneity, resistance mechanisms, and off-target toxicities persist. By integrating advances in conjugation chemistry, linker engineering, and payload selection, next-generation ADCs are poised to expand efficacy and safety in hematologic oncology and further refine targeted therapy in blood cancers."

Journal • Hematological Disorders • Hematological Malignancies • Oncology

Pattern of infections and impact on immunocompetence of next generation B-cell depleting immunotherapies in non-Hodgkin's lymphomas: Results from a multicentre retrospective real- life cohort. (ASH 2025) - "All patients diagnosed with NHL in three Italian centers, who started thetreatment from Dec 1st, 2019 to Apr 30th, 2025 were consecutively included in the analysis. 110 NHL patients were treated with 131 lines of immunotherapies, including 91 with antiCD19CAR-T cells (46 Axi-cel, 29 Tisa-cel, 16 Brexu-cel), 30 with antiCD20/antiCD3 bispecific MoAbs (10glofitamab, 14 epcoritamab and 6 mosunetuzumab), and 10 with AntiCD19 ADC (loncastuximab). Infections are common complications during novel immunotherapy treatments in NHL:nonetheless, in our real-life cohort most of cases occurred early (< 100 days) and showed manageablemild-moderate severity. Overall, in this setting of relapsed/refractory NHL patients the main cause ofdeath remains lymphoma progression."

Retrospective data • Dermatology • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Immunology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Mediastinal Large B-Cell Lymphoma • Respiratory Diseases

EPCOR+LONCA: Epcoritamab in Combination With Loncastuximab Tesirine in Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P2 | N=26 | Recruiting | Sponsor: University of Miami | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Trials in progress - A phase I study of loncastuximab tesirine and rituximab following stereotactic radiosurgery in patients with primary and secondary central nervous system lymphomas (SOLAR) (ASH 2025) - P1 | "Exploratory endpoints include duration of response, progression-free survival, and overall survival. Correlative analysis includes minimal residual disease testing on banked diagnostic tissue and CSF from different timepoints."

Clinical • P1 data • Surgery • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • CNS Disorders • CNS Lymphoma • CNS Tumor • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma