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

Cutaneous toxicities to antibody-drug conjugate loncastuximab tesirine: A multicenter retrospective analysis (EADV 2025) - No abstract available

Retrospective data • Oncology

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

Follicular Lymphoma: Current Therapeutic Landscape and Future Prospects (ICML 2025) - P3 | "The ability of maintenance rituximab, obinutuzumab induction, or bendamustine-based induction to lower early progression rates without affecting OS or HT rate [10, 12, 18] suggests that not all POD24 cases are equal, with a subset remaining resistant to current treatments...Since 2021, three CAR-T constructs—axicabtagene-ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—and three CD3 × CD20 BsAbs—mosunetuzumab, epcoritamab, and odronextamab—have gained regulatory approval in Europe and/or US as options for third line and later...Loncastuximab tesirine (CD19-directed ADC) shows promising activity in 2L+ R/R FL (CR 67%, manageable toxicity in a small Phase 2 cohort) [40]. Adding tafasitamab, an anti-CD19 antibody, to R2 in R/R FL patients improved PFS by 57% in the inMIND trial after a median follow-up of 14 months [41]...However, the ROSEWOOD trial showed obinutuzumab-zanubrutinib was superior to Obinutuzumab alone..."

IO biomarker • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • EZH2 • IGH

A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL (clinicaltrials.gov) - P1/2 | N=46 | Active, not recruiting | Sponsor: Mitsubishi Tanabe Pharma Corporation | Recruiting ➔ Active, not recruiting

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

T-Cell Redirecting Strategies in Large B-Cell Lymphoma and Follicular Lymphoma (ICML 2025) - "The randomized STARGLO trial compared the combination of glofitamab with gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx, meeting its primary endpoint of OS in favor of the experimental arm (HR 0.62 [95% CI 0.43–0.88])...Other treatment options to consider in this R/R patient population are tafasitamab/lenalidomide [107], loncastuximab tesirine [108] and rituximab-bendamustine-polatuzumab [109], amongst others...Three CAR-T constructs are available based on Phase 2, single-arm trials, namely ZUMA-5 (axi-cel), ELARA (tisa-cel), and TRANSCEND-FL (liso-cel)...Mosunetuzumab, epcoritamab and odronextamab received regulatory approval (U.S...She started treatment with a bispecific antibody, aiming to carry out her first imaging assessment after three cycles. Permission to Reproduce Material From Other Sources The author has nothing to report."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD19

Loncastuximab Tesirine and Rituximab as Bridging Therapy Prior to Standard-of-care CD19 CAR T-cell Therapy in Patients With Large B-cell Lymphoma (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: University of Utah | Not yet recruiting ➔ Recruiting

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

“Based on the review of the data on safety and efficacy, the benefit-risk balance of Zynlonta (loncastuximab tesirine) in the approved indication(s) remains unchanged” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 5 – 8 May 2025: “Nevertheless, the product information should be updated to add sepsis as a warning and as an undesirable effect with a frequency ‘common’. Therefore, the current terms of the marketing authorization(s) should be varied”

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

Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: drug profile and expert opinion on the prevention and management of adverse events. (PubMed, Leuk Lymphoma) - "While loncastuximab has an overall manageable safety profile, it may cause drug-specific adverse events (AEs) different from other R/R DLBCL treatments. After summarizing the profile of loncastuximab, here we discuss PBD-specific AEs such as phototoxicity & cutaneous reactions, edema & effusions, and liver enzyme elevation; and use available clinical trial data, real-world evidence and clinical scenarios to provide expert opinion and practical advice on how to prevent and manage these non-hematological, PBD-specific AEs."

Adverse events • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

PHASE Ib CLINICAL TRIAL OF LONCASTUXIMAB TESIRINE AND ROFLUMILAST IN ADDED TO R-CHOP (Lo-RR-CHOP) FOR TREATMENT NAIVE HIGH RISK DIFFUSE LARGE B CELL LYMPHOMA (ICML 2025) - "While polatuzumab vedotin plus R-CHP improves PFS without OS benefit, its real-world applicability remains uncertain. Safety evaluations include serial laboratory testing, echocardiography and ECG monitoring. The trial is actively enrolling patients, with preliminary safety and efficacy data to be presented."

Clinical • IO biomarker • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

AUSTRALIAN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA FREQUENTLY FAIL ELIGIBILITY CRITERIA FOR LANDMARK AND REGISTRATION CLINICAL TRIALS (ICML 2025) - "More than 7 new therapies have been approved for rDLBCL since 2010 based on registrational trials, for example, tafasitamab-lenalidomide (Salles, 2020), polatuzumab plus bendamustine and rituximab (Sehn, 2020), selinexor (Kalakonda, 2020), loncastuximab (Caimi, 2021) and 3 CAR-T products. Most rDLBCL pts are ineligible for registrational trials, causing difficulty applying results to routine care. Significant variation in rates of eligibility exists across landmark registration trials, causing challenges in comparisons in the absence of randomised studies. Standardised eligibility criteria are desperately needed for registrational studies and should more closely reflect the rDLBCL population being considered for these agents."

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

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

UPDATED ANALYSIS OF A PHASE 2 MULTICENTER STUDY OF THE LONCASTUXIMAB IN RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA DEMONSTRATES HIGH RATE OF COMPLETE RESPONSES (ICML 2025) - P2 | "Lonca treatment demonstrates clinically meaningful activity with robust CR rate in r/r MZL patients, exceeding the predefined futility threshold set for analysis following response assessment in 40 patients."

Clinical • P2 data • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

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) (EHA 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 • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • CD20 • CD4 • CD8 • IL6

UPDATED SAFETY RUN-IN RESULTS FROM LOTIS-5: A PHASE 3, RANDOMIZED TRIAL OF LONCASTUXIMAB TESIRINE WITH RITUXIMAB VERSUS IMMUNOCHEMOTHERAPY IN PATIENTS WITH R/R DLBCL/HGBL (EHA 2025) - P3 | "Aims: LOTIS-5 (NCT04384484) is evaluating Lonca-R vs R+gemcitabine+oxaliplatin in transplant-ineligible pts with R/R DLBCL/HGBL. In this updated safety run-in of LOTIS-5, fixed treatment duration of Lonca-R showed no new safety signals and demonstrated encouraging antitumor activity, with signs of durable response in R/R DLBCL/HGBL pts maintained >28 months after EOT. Lonca-R resulted in a lower median Cmax than monotherapy in C1; Ctrough was comparable. ADA testing showed no positivity."

Clinical • P3 data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • CD19

ADC Therapeutics Announces Updated ZYNLONTA Investigator-Initiated Trial Data in R/R Marginal Zone Lymphoma Presented at 18th International Conference on Malignant Lymphoma (ICML) (PRNewswire) - P2 | N=50 | NCT05296070 | "As of February 10, 2025, a total of 27 adult patients with r/r MZL and previously treated with ≥1 line of systemic therapy were enrolled with 26 patients evaluable for response. Highlights of the data include: Overall response rate (ORR) of 84.6% (22/26); complete response (CR) rate of 69.2% (18/26); Among POD24 patients assessed for response, a CR rate of 61.5% (8/13) was observed; CR was maintained in 17 of 18 CR patients who achieved CR, with longest duration of CR of 27 months from start of treatment; Progression-free survival (PFS) was 92.9% at 12 months; 27 enrolled patients experienced adverse events (AE), consistent with the known safety profile of ZYNLONTA and most commonly grade 1 or 2. Grade 3 and 4 AEs were observed in 16 and 2 patients, respectively and included neutropenia, RSV lung infection and hyponatremia (with 2 AEs occurring in the same patient)."

P2 data • Marginal Zone Lymphoma

ADC Therapeutics Announces $100 Million Private Placement Extending Expected Cash Runway into 2028 (PRNewswire) - "ADC Therapeutics SA...announced that it has entered into securities purchase agreements for the sale of its equity securities to certain institutional investors in a $100.0 million private investment in public equity ('PIPE') financing....Gross proceeds from the PIPE financing are anticipated to be approximately $100.0 million before deducting placement agent fees and offering expenses....ADC Therapeutics intends to use the net proceeds from the PIPE to fund multiple catalysts primarily in support of ZYNLONTA clinical development as well as ZYNLONTA commercialization activities, working capital and general corporate purposes....Beyond ZYNLONTA, the Company will advance its preclinical exatecan-based ADC targeting prostate-specific membrane antigen (PSMA) and will discontinue early development efforts for the remaining preclinical programs in solid tumors."

Discontinued • Financing • Diffuse Large B Cell Lymphoma • Solid Tumor

ADC Therapeutics Announces Updated Data from LOTIS-7 Clinical Trial Presented at the European Hematology Association 2025 Congress (ADC Therapeutics Press Release) - P1b | N=200 | LOTIS-7 (NCT04970901) | Sponsor: ADC Therapeutics S.A. | "ZYNLONTA in combination with glofitamab (COLUMVI) in patients with r/r DLBCL demonstrated clinically meaningful benefit with overall response rate (ORR) of 93.3% and a complete response (CR) rate of 86.7% across 30 efficacy evaluable patients; 25 of 26 patients achieving CR remained in CR as of the data cut-off; Initial data show the combination is generally well tolerated with a manageable safety profile; Company expanding enrollment for LOTIS-7 to 100 patients at 150 µg/kg dose"

P1 data • Trial status • Diffuse Large B Cell Lymphoma

The anticipated catalysts within the cash runway… (PRNewswire) - "(i) LOTIS-7: Fuller, more mature data in the dose expansion arm of LOTIS-7 Phase 1b trial of ZYNLONTA plus glofitamab in patients with relapsed/refractory...DLBCL expected in second half of 2025; Expanding enrollment to 100 patients at recommended dose, with full enrollment expected in first half of 2026; Potential publication and compendia inclusion in first half of 2027; (ii) LOTIS-5: Expect to reach pre-specified number of...PFS events by end of 2025; Topline results from the LOTIS-5 Phase 3 confirmatory trial evaluating ZYNLONTA in combination with rituximab in patients with r/r DLBCL anticipated in late 2025 or first half of 2026; Potential biologics license application submission to regulatory authorities in first half of 2026 with potential confirmatory approval in 2L+ DLBCL and publication and compendia inclusion in first half of 2027; (iii) Indolent Lymphomas: Potential r/r marginal zone lymphoma publication and compendia inclusion in first half of 2027."

Clinical data • FDA filing • Trial status • US reimbursement • Diffuse Large B Cell Lymphoma • Marginal Zone Lymphoma

QSP modeling of loncastuximab tesirine with T-cell-dependent bispecific antibodies guides dose-regimen strategy. (PubMed, NPJ Syst Biol Appl) - P1 | "Clinically validated models of the ADC loncastuximab tesirine and TDB mosunetuzumab were combined and extended to additional TDBs (glofitamab and epcoritamab). Additive antitumor effects were predicted from the fourth cycle onward, with combination efficacy insensitive to loncastuximab tesirine dose reductions or patient lymphopenias. Results of the LOTIS-7 study (NCT04970901) will soon be available to assess these predictions."

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

Antibody-Directed Cell Internalization of Targeted Covalent Europium Tag Enables In Situ Kinase Labeling and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Quantification. (PubMed, Anal Chem) - "Based on this strategy, we constructed a multifunctional antibody-targeted covalent Ln tag (Ab-TC-Ln, LTX-VC-Ibt-DOTA-Eu), comprising a cell-permeable monoclonal antibody (Loncastuximab, LTX), a targeted covalent Ln tag (Ibt-DOTA-Eu) for Bruton's tyrosine kinase (BTK), and between them a cathepsin B-cleavable linker (VC). LTX-TC-Ln enables cancer cell recognition, internalization, release of targeted covalent element tags, and specific labeling of Ln to intracellular BTK for ICP-MS quantification. Our work establishes a promising antibody-directed cell internalization strategy for intracellular protein Ln labeling and quantification, which will inspire the development of new ICP-MS approaches toward the quantification of other important protein targets in the future."

Journal • Oncology • BTK • CTSB

A Review of NICE UK Submissions for Antibody-Drug Conjugates in Oncology (ISPOR 2025) - "All of these ADCs were assessed by NICE from inception to 2024 12 FDA-approved ADCs were identified: Trastuzumab emtansine, Trastuzumab deruxtecan, Sacituzumab govitecan, Inotuzumab ozogamicin, Polatuzumab vedotin, Loncastuximab tesirine, Tisotumab vedotin, Enfortumab vedotin, Mirvetuximab soravtansine-gynx, Belantamab mafodotin-blmf, Gemtuzumab ozogamicin, and Brentuximab vedotin. In conclusion, ADCs have revolutionized cancer treatment with their targeted delivery and significant therapeutic benefits. The evolution of ADCs since 2000 highlights their potential in both refractory and early-stage diseases. Continued advancements in ADC design and technology promise even greater therapeutic efficacy."

NICE • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Breast Cancer • Cervical Cancer • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Apr 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • CD20

Real-world treatment of large B-cell lymphoma with chimeric antigen receptor T-cell therapy after loncastuximab tesirine: a plain language summary. (PubMed, Future Oncol) - No abstract available

HEOR • Journal • Real-world evidence • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

How well does loncastuximab tesirine work after chimeric antigen receptor T-cell treatment in diffuse large B-cell lymphoma? A plain language summary of a real-world evidence study. (PubMed, Future Oncol) - No abstract available

HEOR • Journal • Real-world evidence • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab Tesirine in WM (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Shayna Sarosiek, MD | Trial completion date: Aug 2027 ➔ Aug 2028 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia • CXCR4 • MYD88