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)

Last updated: June 16, 2025
Sponsor: ADC Therapeutics S.A.
Overall Status: Active - Recruiting

Phase

1

Condition

Lymphoma, B-cell

Lymphoma

Treatment

Mosunetuzumab

Glofitamab

Polatuzumab Vedotin

Clinical Study ID

NCT04970901
ADCT-402-105
2021-001071-16
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Male or female participant aged 18 years or older

  • Pathologic diagnosis of relapsed (disease that has recurred following a response) orrefractory (disease that failed to respond to prior therapy) B-NHL (2016 WorldHealth Organization classification) who have failed, or been intolerant to anyapproved therapy and had received at least two systemic treatment regimens indose-escalation part; and at least one systemic treatment regimen in dose-expansionpart

  • Aggressive B Cell Lymphomas:

  • DLBCL (including transformed diseases, but for Arms E and F, includingtransformed FL only)

  • HGBCL

  • FL Grade 3b

  • Indolent NHL:

  • FL (Grade 1-3a)

  • MZL

  • For Arm C only:

  • 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 theinvestigator, 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

  • Adequate organ function

  • Women of childbearing potential (WOCBP) must agree to use a highly effective methodof contraception from the time of giving informed consent until at least 10 monthsafter the last dose of loncastuximab tesirine. Men with female partners who are ofchildbearing potential must agree to use a condom when sexually active or practicetotal abstinence from the time of giving informed consent the first dose until atleast 7 months after the last dose of loncastuximab tesirine. Men must refrain fromdonating sperm during this same period. For the arm that includes glofitamab, WOCBPmust agree to use contraceptive methods that result in a failure of less than 1% peryear or remain abstinent (refrain from heterosexual intercourse) during thetreatment period and for at least 18 months after pretreatment with obinutuzumab.For the arm that includes mosunetuzumab, WOCBP must agree to use contraceptivemethods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable).

Exclusion

Exclusion Criteria:

  • Known history of hypersensitivity resulting in treatment discontinuation to orpositive serum human ADA to a CD19 antibody

  • Previous therapy with loncastuximab tesirine

  • Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied torelevant arm and/or cohort of the specific drug administered)

  • Participants who received previous treatment of polatuzumab vedotin containingregimen will be excluded from Arm C

  • Participants who received previous treatment of glofitamab containing regimenwill be excluded from Arm E

  • Participants who received previous treatment of mosunetuzumab containingregimen will be excluded from Arm F

  • Allogenic or autologous stem cell transplant within 60 days prior to start of studydrug (C1 D1)

  • Human immunodeficiency virus (HIV) seropositive

  • Serologic evidence of chronic hepatitis B virus (HBV) infection and unable orunwilling to receive standard prophylactic antiviral therapy or with detectable HBVviral load

  • Serologic evidence of hepatitis C virus (HCV) infection without completion ofcurative treatment or with detectable HCV viral load

  • History of confirmed progressive multifocal leukoencephalopathy

  • History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophageactivation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)

  • Lymphoma with active central nervous system (CNS) involvement at the time ofscreening, including leptomeningeal disease

  • Clinically significant third space fluid accumulation (i.e., ascites requiringdrainage or pleural effusion that is either requiring drainage or associated withshortness 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), except shorter if approved by theSponsor

  • 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 (Grade ≤2 alopecia) due toprevious 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 carcinomain situ of the breast, or other malignancy that the Sponsor's medical monitor andInvestigator 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 CNS lymphoma or leptomeningeal infiltration

  • Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, orneurodegenerative disease

  • Known active infection, reactivation of a latent infection, whether bacterial,viral, fungal, mycobacterial, or other pathogens (excluding fungal infections ofnail beds), or any major episode of infection requiring hospitalization or treatmentwith intravenous (IV) antibiotics within four weeks prior to C1D1

  • Active or history of autoimmune disease or immune deficiency, motor neuropathyconsidered of autoimmune origin and other central nervous system (CNS) autoimmunediseases, including but not limited to, myasthenia gravis, myositis, autoimmunehepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory boweldisease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögrensyndrome, Guillain-Barré syndrome, or multiple sclerosis, with, with certainexceptions

  • Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinaseinhibitors, systemic immunotherapeutic/immunostimulating agents, including, but notlimited to, cluster of differentiation 137 agonists or immune checkpoint blockadetherapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4),anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines andmonoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate,thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or fivehalf-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of needfor systemic immunosuppressive medication during study treatment, with certainexceptions

  • Prior treatment with CAR-T-cell therapy within 100 days prior to C1D1; primaryrefractory patients (progressive or persistent disease within 30 days) to CAR-T-celltherapy are not eligible.

  • Toxicities from prior anti-cancer therapy including immunotherapy that did notresolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed withreplacement therapy and stable vitiligo

  • Any history of immune-related Grade ≥3 AE with the exception of endocrinopathymanaged with replacement therapy

  • Ongoing corticosteroid use greater than 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment

  • Administration of a live attenuated vaccine within 4 weeks prior to the first doseof study treatment or anticipation that such a live attenuated vaccine will berequired during the study or within 5 months after last dose of study treatment

Extra Exclusion Criteria for Arm E (includes glofitamab) only.

• Known history of hypersensitivity to obinutuzumab

Study Design

Total Participants: 200
Treatment Group(s): 5
Primary Treatment: Mosunetuzumab
Phase: 1
Study Start date:
June 17, 2022
Estimated Completion Date:
December 18, 2026

Study Description

This is a Phase 1b, multi-center, open-label, multi-arm study to evaluate the safety and anti-cancer activity of loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or mosunetuzumab in participants with relapsed or refractory B-cell Non-Hodgkin Lymphoma (R/R B-NHL). The study will enroll approximately 200 participants.

Loncastuximab tesirine (ADCT-402; Zynlonta) is an antibody drug conjugate (ADC), composed of a humanized monoclonal antibody directed against human cluster of differentiation 19 (CD19) conjugated through a cathepsin-cleavable linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Loncastuximab tesirine has been granted by Food and Drug Administration (FDA) as accelerated approval for adult participants with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma (HGBCL). In the European Union (EU), the European Commission (EC) granted conditional approval for the treatment of adult patients with relapsed or refractory DLBCL and HGBCL, after two or more lines of systemic therapy.

The study includes multiple arms in two parts, Dose Escalation part (Part 1) and Dose Expansion part (Part 2). In Part 1, for the arm of loncastuximab tesirine in combination with polatuzumab vedotin includes DLBCL, HGBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and Burkitt lymphoma (BL); for the arms of loncastuximab tesirine in combination with glofitamab or mosunetuzumab include DLBCL, HGBCL, FL, and MZL. In Part 2, participants will be treated at the dose level determined from Part 1. The Sponsor will conduct the safety monitoring and the overall supervision of the study in consultation with the Dose-Escalation Steering Committee (DESC).

For each participant, the study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 21 days), and a Follow-up Period (approximately every 12 week visits for up to two years). Participants may continue treatment for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

Treatment with gemcitabine (Arm A), lenalidomide (Arm B), and umbralisib (Arm D) were removed.

Connect with a study center

  • Universitair Ziekenhuis Gent

    Gent, 9000
    Belgium

    Active - Recruiting

  • Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne

    Yvoir, B-5530
    Belgium

    Active - Recruiting

  • Fakultni Nemocnice Brno

    Brno, South Moravian 625 00
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Ostrava

    Ostrava, 708 52
    Czechia

    Active - Recruiting

  • Fakultni nemocnice v Motole

    Prague, 150 06
    Czechia

    Active - Recruiting

  • Fakultní Nemocnice Královské Vinohrady

    Prague, 100 34
    Czechia

    Active - Recruiting

  • Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII

    Bergamo, 24127
    Italy

    Active - Recruiting

  • Centro di Ricerche Cliniche - IRCCS Azienda Ospedaliero Universitaria di Bologna

    Bologna, 40138
    Italy

    Active - Recruiting

  • Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia

    Brescia, 25123
    Italy

    Active - Recruiting

  • Istituto Europeo di Oncologia

    Milano, 20141
    Italy

    Active - Recruiting

  • Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

    Barcelona, 08908
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007
    Spain

    Active - Recruiting

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034
    Spain

    Active - Recruiting

  • Complejo Asistencial Universitario de Salamanca - Hospital Clínico

    Salamanca, 37007
    Spain

    Active - Recruiting

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026
    Spain

    Active - Recruiting

  • University College London Hospitals NHS Foundation Trust

    London, NW1 2PG
    United Kingdom

    Completed

  • Oxford University Hospitals NHS Foundation Trust

    Oxford, OX3 7LE
    United Kingdom

    Completed

  • University of California San Francisco - Fresno Center for Medical Education and Research

    Clovis, California 93611
    United States

    Active - Recruiting

  • Scripps Health - Prebys Cancer Center

    San Diego, California 92103
    United States

    Active - Recruiting

  • Miami Cancer Institute

    Miami, Florida 33176
    United States

    Active - Recruiting

  • Sylvester Comprehensive Cancer Center

    Miami, Florida 33136
    United States

    Active - Recruiting

  • Memorial Cancer Institute - Memorial Hospital West

    Pembroke Pines, Florida 33028
    United States

    Active - Recruiting

  • The Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia 30342
    United States

    Active - Recruiting

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Mission Cancer + Blood - Mission Cancer Foundation

    Des Moines, Iowa 50309
    United States

    Active - Recruiting

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • University of Minnesota

    Minneapolis, Minnesota 55455
    United States

    Active - Recruiting

  • Columbia University Irving Medical Center

    New York, New York 10027
    United States

    Active - Recruiting

  • Cleveland Clinic Main Campus

    Cleveland, Ohio 44195
    United States

    Active - Recruiting

  • Oregon Health and Science University

    Portland, Oregon 97239
    United States

    Active - Recruiting

  • Penn Medicine - Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Allegheny Health Network - West Penn Hospital

    Pittsburgh, Pennsylvania 15224
    United States

    Active - Recruiting

  • Brown University Health - Rhode Island Hospital

    Providence, Rhode Island 02903
    United States

    Active - Recruiting

  • Hollings Cancer Center

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Avera Cancer Institute

    Sioux Falls, South Dakota 57105
    United States

    Site Not Available

  • Greco-Hainsworth Tennessee Oncology Centers for Research (GHCR)

    Nashville, Tennessee 37203
    United States

    Active - Recruiting

  • Baylor University Medical Center

    Dallas, Texas 75246
    United States

    Active - Recruiting

  • Huntsman Cancer Institute

    Salt Lake City, Utah 84112
    United States

    Active - Recruiting

  • Emily Couric Clinical Cancer Center

    Charlottesville, Virginia 22903
    United States

    Active - Recruiting

  • NEXT Virginia (Virginia Cancer Specialists)

    Fairfax, Virginia 22031
    United States

    Site Not Available

  • Froedtert & Medical College of Wisconsin

    Milwaukee, Wisconsin 53226
    United States

    Active - Recruiting

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