A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)

Running, not enrolling · Phase 1

Conditions studied: B-Cell Non-Hodgkin Lymphoma, Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma

In brief

The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or mosunetuzumab, and to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the combinations.

Key facts

Study ID

NCT04970901

Run by

ADC Therapeutics S.A.

People needed

154

Starts

2022-06-17

Expected to finish

2028-04-30

Last updated by the study team

2026-07-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female participant aged 18 years or older
• Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) B-NHL (2016 World Health Organization classification) who have failed, or been intolerant to any approved therapy and had received at least two systemic treatment regimens in Part 1; and at least one systemic treatment regimen in Part 2
• LBCL:
• Part 2 Arm E enrollment focused on LBCL only
• DLBCL, not otherwise specified (NOS)
• Germinal Center B-cell type
• Activated B-cell type
• Transformed FL (note: patients with transformed FL must have received at least one line of systemic therapy post-transformation to be eligible)
• HGBCL, with MYC and BCL2 and/or BCL6 rearrangements
• HGBCL, NOS
• FL Grade 3b
• Arm F and Part 1 Arm E:
• All LBCL histologies listed above
• FL (Grade 1-3a)
• MZL
• For Arm C only:
• All histologies listed above
• DLBCL (including transformed diseases)
• MCL
• BL
• Life expectancy of at least 24 weeks according to Investigator's judgement
• Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. FL and MZL)
• Measurable disease as defined by the 2014 Lugano Classification
• Availability of formalin-fixed paraffin-embedded tumor tissue block
• ECOG performance status 0 to 2

You may not qualify if…

• Known history of hypersensitivity resulting in treatment discontinuation to or positive serum human ADA to a CD19 antibody
• Previous therapy with loncastuximab tesirine
• Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied to relevant arm and/or cohort of the specific drug administered)
• Participants who received previous treatment of polatuzumab vedotin containing regimen will be excluded from Arm C
• Participants who received previous treatment of glofitamab containing regimen will be excluded from Arm E
• Participants who received previous treatment of mosunetuzumab containing regimen will be excluded from Arm F
• Human immunodeficiency virus (HIV) seropositive
• Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
• Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
• History of confirmed progressive multifocal leukoencephalopathy
• History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)/immune effector cell associated HLH-like syndrome (IEC-HS)
• Existing pericardial effusion (any grade) or clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
• Breastfeeding or pregnant
• Significant medical comorbidities
• Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), unless approved by the Sponsor
• Live vaccine within 4 weeks prior to C1D1
• Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (excluding alopecia) due to previous therapy prior to screening
• Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary
• Extra Exclusion Criteria for Arms E (includes glofitamab) and F (includes mosunetuzumab) Note: as applicable, the arm-specific exclusion criteria may supersede the general ones, such as stem cell transplant.
• Prior allogeneic stem cell transplant and solid organ transplant
• Autologous stem cell transplant within 100 days prior to C1D1
• History of central nervous system (CNS) lymphoma or leptomeningeal infiltration
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known active infection, reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within four weeks prior to C1D1
• Active or history of autoimmune disease or immune deficiency, motor neuropathy considered of autoimmune origin and other CNS autoimmune diseases, including but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with, with certain exceptions

Where it is running

• University of California San Francisco - Fresno Center for Medical Education and Research — Clovis, California, United States
• Scripps Health - Prebys Cancer Center — San Diego, California, United States
• Sylvester Comprehensive Cancer Center — Miami, Florida, United States
• Miami Cancer Institute — Miami, Florida, United States
• Memorial Cancer Institute - Memorial Hospital West — Pembroke Pines, Florida, United States
• Winship Cancer Institute of Emory University — Atlanta, Georgia, United States
• The Blood and Marrow Transplant Group of Georgia — Atlanta, Georgia, United States
• Mission Cancer + Blood - Mission Cancer Foundation — Des Moines, Iowa, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• University of Minnesota — Minneapolis, Minnesota, United States
• Columbia University Irving Medical Center — New York, New York, United States
• Cleveland Clinic Main Campus — Cleveland, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Penn Medicine - Perelman Center for Advanced Medicine — Philadelphia, Pennsylvania, United States
• Allegheny Health Network - West Penn Hospital — Pittsburgh, Pennsylvania, United States
• Brown University Health - Rhode Island Hospital — Providence, Rhode Island, United States
• Hollings Cancer Center — Charleston, South Carolina, United States
• Greco-Hainsworth Tennessee Oncology Centers for Research (GHCR) — Nashville, Tennessee, United States
• Baylor University Medical Center — Dallas, Texas, United States
• Huntsman Cancer Institute — Salt Lake City, Utah, United States
• Emily Couric Clinical Cancer Center — Charlottesville, Virginia, United States
• NEXT Virginia (Virginia Cancer Specialists) — Fairfax, Virginia, United States
• Froedtert & Medical College of Wisconsin — Milwaukee, Wisconsin, United States
• Universitair Ziekenhuis Gent — Ghent, Belgium

Full record on ClinicalTrials.gov

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