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

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

Management of Diffuse Large B-Cell Lymphoma as Post-Transplant Lymphoproliferative Disorder in a Kidney Transplant Recipient: A Case Report. (PubMed, Hematol Rep) - "Salvage therapies, including polatuzumab vedotin and rituximab, achieved remission...Single-agent rituximab was insufficient, but combination chemotherapy and novel agents like loncastuximab tesirine were effective. Balancing oncologic control and graft preservation remains critical. This case highlights the need for individualized approaches and novel therapies in managing PTLD while addressing the complexities of immunosuppression and organ preservation."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Organ Transplantation • Transplant Rejection • Transplantation • CD20

Loncastuximab and Roflumilast Added to R-CHOP (Lo-RR-CHOP) for Naïve High-Risk Diffuse Large B-cell Lymphoma (DLBCL) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio

New P1 trial • 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) (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

The potential of antibody-drug conjugates for effective therapy in diffuse large B-cell lymphoma. (PubMed, Expert Opin Biol Ther) - "Both polatuzumab vedotin and loncastuximab tesirine are established as useful therapeutics options, with polatuzumab vedotin currently approved in first line and relapsed/refractory setting, while loncastuximab tesirine is approved in relapsed setting. ADCs are effective with tolerable safety profile and currently many more ADCs are undergoing clinical trials."

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

Loncastuximab Tesirine and Rituximab Following Stereotactic Radiosurgery (SRS) in Patients With Primary and Secondary Central Nervous System Lymphomas (Lonca-R After SRS in CNSL) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: University of Utah | Initiation date: Dec 2024 ➔ Mar 2025

Trial initiation date • CNS Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

ADC Therapeutics Reports First Quarter 2025 Financial Results and Provides Operational Update (PRNewswire) - "Abstract accepted for presentation of marginal zone lymphoma (MZL) data at ICML. A poster entitled, "Updated analysis of a phase 2 multicenter study of the loncastuximab in relapsed/refractory marginal zone lymphoma demonstrates high rate of complete responses" will be presented at ICML....Discontinuation of ADCT-602 trial. Based on the available clinical data, the Phase 1/2 ADCT-602 clinical trial, sponsored by The University of Texas MD Anderson Cancer Center, evaluating ADCT-602 in patients with r/r B-cell acute lymphoblastic leukemia will be discontinued....Product Revenues: ZYNLONTA generated net product revenues of $17.4 million for the first quarter of 2025 as compared to $17.8 million for the first quarter of 2024."

P2 data • Sales • Trial termination • B Acute Lymphoblastic Leukemia • Marginal Zone Lymphoma

ADC Therapeutics Reports First Quarter 2025 Financial Results and Provides Operational Update (PRNewswire) - "Enrollment of 40 patients reached in LOTIS-7 dose expansion arm. Forty patients have been enrolled in the dose expansion arm of the Phase 1b clinical trial evaluating the safety and efficacy of ZYNLONTA in combination with the bispecific antibody glofitamab in patients with r/r DLBCL. The Company expects to provide an update on the LOTIS-7 trial in the second half of 2025....LOTIS-5 remains on track to reach prespecified progression-free survival (PFS) events by end of 2025. After the prespecified number of PFS events is reached and data are available, the Company expects to provide topline data on the Phase 3 confirmatory trial evaluating ZYNLONTA in combination with rituximab in patients with 2L+ DLBCL."

P1 data • P3 data: top line • Trial status • Diffuse Large B Cell Lymphoma

ADC Therapeutics Announces Presentation of LOTIS-7 Clinical Trial Data at the European Hematology Association 2025 Congress (EHA2025) and the 18th International Conference on Malignant Lymphoma (ICML) (PRNewswire) - P1 | N=200 | LOTIS-7 (NCT04970901) | Sponsor: ADC Therapeutics S.A. | "ADC Therapeutics SA...announced data presentations from the LOTIS-7 Phase 1b clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) in combination with glofitamab in patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL)....Updated LOTIS-5 safety run-in data evaluating the combination of ZYNLONTA plus rituximab (Lonca-R) will also be featured at EHA2025....In the efficacy evaluable population, overall response rate (ORR) was 95.5% (21/22), complete response (CR) rate was 90.9% (20/22), and median duration of response (DOR) was not reached. Among 31 patients treated, the combination demonstrated a manageable safety profile. Adverse events were consistent with known profiles of the individual agents, with neutropenia (32.3%) being the most common Grade ≥3 treatment-emergent adverse event (TEAEs)."

P1 data • P3 data • Diffuse Large B Cell Lymphoma

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) - No abstract available

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

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 (DLBCL) (ICML 2025) - No abstract available

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

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) - No abstract available

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

proPBD-ADCs: optimization of therapeutic potential of ADCs based on capped PBD payload with attenuated potency (AACR 2025) - "In April 2021, the FDA approved the first PBD-based ADC, the CD19 targeting loncastuximab tesirine, for treatment of adult patients with relapsed or refractory large B-cell lymphoma, including DLBCL, after 2 or more lines of therapy...Complemented by a broad choice of payloads with various mode-of-action (toxSYN® platform), these joint technologies have been applied in multiple clinical programs up to phase 3.Our strategy to optimize the therapeutic potential of PBD-ADCs that incorporate GlycoConnect® and HydraSpace® technology further, is two-fold: (a) apply PBD dimer payload with reduced potency versus common clinical structures and (b) incorporate a pro-drug concept (proPBD-ADC) by shielding the PBD payload by a capping structure that is stable in circulation but at the same time conditionally released by tumor-associated proteases or under reducing conditions.Data from efficacy studies with HER2-proPBD-ADCs in CDX tumor bearing mouse models will be..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • HER-2

Response to Michelerio et al. regarding "Antibody-drug conjugates: A review of cutaneous adverse effects". (PubMed, J Am Acad Dermatol) - No abstract available

Adverse events • Journal • Oncology

Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: University of Washington | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Response to Saberi SA et al.'s "Antibody-drug conjugates: A review of cutaneous adverse effects". (PubMed, J Am Acad Dermatol) - No abstract available

Adverse events • Journal • Dermatology • Oncology

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 | Recruiting | Sponsor: Istituto Clinico Humanitas

IO biomarker • New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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

New P2 trial • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Budget impact of introducing glofitamab for treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy in the United States. (PubMed, J Med Econ) - "Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine, polatuzumab vedotin + bendamustine + rituximab, rituximab + gemcitabine + oxaliplatin, tafasitamab + lenalidomide, and epcoritamab (Epcor). Across all sensitivity analyses, the inclusion of glofitamab had minimal PMPM budget impact, ranging from -$0.0256 to -$0.0108. With the lowest 3-year total cost per treated patient among the newer therapies, glofitamab being an available option in the 3L + DLBCL market is estimated to save a hypothetical 1,000,000-member health plan $728,697 in cumulative total costs and $0.0202 in PMPM costs over 3 years."

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