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) (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

LOTIS 5: Study to Evaluate Loncastuximab Tesirine With Rituximab Versus Immunochemotherapy in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P3 | N=440 | Active, not recruiting | Sponsor: ADC Therapeutics S.A. | N=228 ➔ 440

Enrollment change • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

THE TOTAL COST OF CARE AND BUDGET IMPACT OF INTRODUCING MOSUNETUZUMAB PLUS POLATUZUMAB VEDOTIN FOR SECOND-LINE OR LATER (2L+) TREATMENT OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (LBCL) TO A UNITED STATES (US) HEALTH PLAN (ISPOR 2026) - P3 | "Comparators included rituximab plus gemcitabine and oxaliplatin (R-GemOx) per the Phase 3 SUNMO trial (NCT05171647) and FDA-approved treatments, including axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), tafasitamab plus lenalidomide (Tafa+len), glofitamab, epcoritamab, loncastuximab tesirine (Lonca), and polatuzumab plus bendamustine and rituximab (Pola-BR). Adding Mosun-Pola to a US payer formulary resulted in a small budget impact that remained robust in OWSA. TCC for Mosun-Pola was lower versus treat-to-progression epcoritamab, Tafa+len and CAR-T regimens. Given the small budget impact and improved clinical outcomes versus R-GemOx demonstrated in the Phase 3 SUNMO trial, Mosun-Pola is a meaningful option for 2L+ relapsed/refractory LBCL."

Clinical • Cost of care • HEOR • B Cell Lymphoma • Hematological Malignancies • Inflammation • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

Cutaneous Adverse Reactions and Antibody-Drug Conjugates: A FAERS 2019-2025 Disproportionality Analysis (AAD 2026) - "CARs were disproportionally reported with enfortumab vedotin (ROR = 3.92 [3.84-4.00] for any CAR and ROR = 3.49 [3.32 – 3.66] for SCAR) and loncastuximab tesirine (ROR = 2.85 [2.47-3.28] for CAR). Although it is still early to report pharmacovigilance data on the newest ADCs, we found early signals of cutaneous adverse events in FAERS with tisotumab vedotin (ROR 1.53 [1.31-1.79] which was approved in 2024. Continued surveillance of this class is important moving forward."

ADC • Steven-Johnson Syndrome • ROR1

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

Fourth Quarter 2025 Operational Updates and Upcoming Milestones (ADC Therapeutics Press Release) - "LOTIS-5 topline results anticipated in 2Q 2026...Assuming positive results, the Company will file a supplemental Biologics License Application (sBLA) submission with the U.S. Food and Drug Administration (FDA), with potential compendia inclusion in the first half of 2027 and confirmatory approval in 2L+ DLBCL to follow in mid-2027...LOTIS-7 trial ongoing with data anticipated by year-end....The Company anticipates publication of data from the University of Miami Sylvester Comprehensive Cancer Center-led multi-center trials of ZYNLONTA in combination with rituximab to treat r/r follicular lymphoma (FL) and as a monotherapy to treat marginal zone lymphoma (MZL) between the end of 2026 and mid-2027. Assuming positive data, the Company intends to assess potential regulatory and compendia pathways."

Clinical data • FDA approval • FDA filing • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Marginal Zone Lymphoma

Management of Primary Refractory Diffuse Large B-Cell Lymphoma in Patients Unsuitable for CAR T-Cell Therapy. (PubMed, Eur J Haematol) - "Conventional platinum-based or gemcitabine- and bendamustine-containing regimens retain a role for short-term disease control but offer limited durability. In contrast, novel antibody-based therapies, including polatuzumab-containing combinations, loncastuximab tesirine, and tafasitamab plus lenalidomide, have expanded treatment options with improved tolerability. Most notably, CD20 × CD3 bispecific antibodies represent a major therapeutic advance, providing off-the-shelf immune engagement with predominantly outpatient administration. From a practical perspective, early identification of reversible barriers to CAR T-cell therapy and timely use of bispecific antibodies or other antibody-based regimens are critical to achieve rapid disease control, preserve organ function, and, when feasible, restore eligibility for cellular therapy."

Journal • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

TREATMENT AFTER CAR T-CELL THERAPY FAILURE IN DIFFUSE LARGE B-CELL LYMPHOMA: HEMATOLOGIST/ONCOLOGISTS' PERSPECTIVES ON ODRONEXTAMAB AND RESULTS FROM THE ELM-1 STUDY (ISPOR 2026) - "Prior to reviewing the ELM-1 study, respondents preferred a BsAb (32.3% epcoritamab; 27.7% glofitamab) or loncastuximab (33.8%) as third-line (3L) treatment for a hypothetical transplant-ineligible patient with R/R DLBCL after 2L CAR T-cell therapy failure. Physicians were receptive to prescribing the BsAb odronextamab, if approved, for patients with R/R DLBCL after failure of CAR T-cell therapy. Nevertheless, concerns about long-term outcomes and logistical hurdles remain, and comparative studies would further understanding of odronextamab's performance relative to other BsAbs approved in this space."

CAR T-Cell Therapy • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

LORELY: Study of Loncastuximab Tesirine in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) Following CAR-T Therapy Failure (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Istituto Clinico Humanitas | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CRP • PIAS4

WWU23_0006: Combining Loncastuximab Tesirine and Epcoritamab in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) (clinicaltrialsregister.eu) - P1/2 | N=104 | Recruiting | Sponsor: Universitaet Muenster

New P1/2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2

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

Dermatologic Adverse Events Associated with Antibody-Drug Conjugate Loncastuximab: A Retrospective Multicenter Cohort Study. (PubMed, J Am Acad Dermatol) - No abstract available

Adverse events • Journal • Retrospective data

ADC Therapeutics Announces Amended HealthCare Royalty Financing Agreement (PRNewswire) - "Based on confidence in the long-term outlook for ZYNLONTA, ADC Therapeutics negotiated mutually beneficial updated terms with HealthCare Royalty, offering greater strategic flexibility to the Company. The new agreement reduces the change of control payment from $750 million to $150 million through the end of 2027, and to $200 million thereafter."

Financing • Diffuse Large B Cell Lymphoma • Large B Cell Lymphoma

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

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

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

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

PRAC adopted updates to Zynlonta (loncastuximab tesirine) product information, confirming its benefit-risk balance remains unchanged. SmPC and Package Leaflet will include a warning for capillary leak syndrome and list cutaneous collagenous vasculopathy as an undesirable effect with unknown frequency, implemented via a marketing authorization variation. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 24 – 27 Nov 2025: [AI generated summary]

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

A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL (clinicaltrials.gov) - P1/2 | N=46 | Active, not recruiting | Sponsor: Tanabe Pharma Corporation | Trial primary completion date: Dec 2025 ➔ Aug 2028

Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

Loncastuximab Tesirine and Venetoclax for Relapsed/ Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: Paolo Caimi, MD | Recruiting ➔ Active, not recruiting | N=36 ➔ 23 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Enrollment change • Enrollment closed • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology