New cocktail of cancer drugs shows promise for tough lymphoma

NCT ID NCT04970901

Disease control Sponsor: ADC Therapeutics S.A. Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jul 17, 2026 · Updated 3 times

Summary

This early-stage study is testing a drug called loncastuximab tesirine (ZYNLONTA) combined with other anti-cancer agents in people whose B-cell non-Hodgkin lymphoma has come back or stopped responding to treatment. The main goal is to find safe doses and see how well the combinations work. About 200 adults aged 18 and older who have tried at least two prior treatments will take part.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: loncastuximab tesirine (ZYNLONTA) combined with polatuzumab vedotin, glofitamab, mosunetuzumab, or obinutuzumab
What this could lead to: If it works, this could point toward a new combination treatment for people with hard-to-treat B-cell non-Hodgkin lymphoma.
What could go wrong: This is a very early (Phase 1) trial with only 200 participants, so it may not lead to a proven treatment. The drug combinations can cause serious side effects, and it is not yet known if they will work better than existing options.

Why investors are watching

ADC Therapeutics is testing its drug loncastuximab tesirine in combination with three other anti-cancer agents for patients with relapsed or refractory B-cell non-Hodgkin lymphoma. For a micro-cap company, this early-phase trial is a key step in expanding the drug's use beyond its current single-agent setting, and the safety and dosing results will shape whether these combinations move forward.

If it works: A positive safety and activity signal could support further development of these combinations, potentially broadening the drug's market reach and strengthening the company's pipeline. Success here might also attract partnership interest or improve the company's negotiating position.

If it fails: Phase 1 trials often fail to show acceptable safety or benefit, and a poor result could stall the program and hurt the company's prospects. Delays in finding the right dose or enrolling patients could also set back timelines and increase costs.

AI-written from the trial record. Speculative, and not investment advice.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

154 people

The number who actually took part.

Started

Jun 2022

Expected to finish

Apr 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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 * Adequate organ function * Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent the first dose until at least 7 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period. Arm E: WOCBP must agree to use contraceptive methods 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 18 months after pretreatment with obinutuzumab. Arm F: WOCBP must agree to use contraceptive methods 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) * Patients 80 years of age and older at the time of signing the informed consent must be deemed fit by Cumulative Illness Rating Scale - Geriatric (CIRS-G scale), defined as no score of 3-4 in any category AND \< 5 categories with a score of 2 excluding hematologic criteria Exclusion Criteria: * 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 * Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinase inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not limited to, cluster of differentiation 137 agonists or immune checkpoint blockade therapies, 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 and monoclonal 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 five half-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of need for systemic immunosuppressive medication during study treatment, with certain exceptions * Prior treatment with CAR-T-cell therapy within 100 days prior to C1D1; primary refractory patients (progressive or persistent disease within 30 days) to CAR-T-cell therapy are not eligible * Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo * Any history of immune-related Grade ≥3 AE with the exception of endocrinopathy managed 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 dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after last dose of study treatment * Arm E only: Known history of hypersensitivity to obinutuzumab

Get updates

Get notified about this study

Vår säkerhetsrekommendation!

Genom att skicka in godkänner du våra Användarvillkor

Conditions

The condition(s) this trial relates to.

B-cell neoplasm B-cell non-Hodgkin lymphoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

B-cell non Hodgkin lymphoma Refractory B-cell non-Hodgkin lymphoma Relapsed B-cell non-Hodgkin lymphoma

Contacts and locations

Locations

Allegheny Health Network - West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States
Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII

Bergamo, 24127, Italy
Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia

Brescia, 25123, Italy
Baylor University Medical Center

Dallas, Texas, 75246, United States
Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States
Brown University Health - Rhode Island Hospital

Providence, Rhode Island, 02903, United States
Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne

Yvoir, B-5530, Belgium
Centro di Ricerche Cliniche - IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, 40138, Italy
Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States
Columbia University Irving Medical Center

New York, New York, 10027, United States
Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, 37007, Spain
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22903, United States
Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia
Fakultni nemocnice v Motole

Prague, 150 06, Czechia
Fakultní Nemocnice Královské Vinohrady

Prague, 100 34, Czechia
Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Greco-Hainsworth Tennessee Oncology Centers for Research (GHCR)

Nashville, Tennessee, 37203, United States
Hollings Cancer Center

Charleston, South Carolina, 29425, United States
Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain
Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain
Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain
Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

Barcelona, 08908, Spain
Istituto Europeo di Oncologia

Milan, 20141, Italy
Memorial Cancer Institute - Memorial Hospital West

Pembroke Pines, Florida, 33028, United States
Miami Cancer Institute

Miami, Florida, 33176, United States
Mission Cancer + Blood - Mission Cancer Foundation

Des Moines, Iowa, 50309, United States
NEXT Virginia (Virginia Cancer Specialists)

Fairfax, Virginia, 22031, United States
Oregon Health and Science University

Portland, Oregon, 97239, United States
Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom
Penn Medicine - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States
Scripps Health - Prebys Cancer Center

San Diego, California, 92103, United States
Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States
The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States
Universitair Ziekenhuis Gent

Ghent, 9000, Belgium
University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom
University of California San Francisco - Fresno Center for Medical Education and Research

Clovis, California, 93611, United States
University of Minnesota

Minneapolis, Minnesota, 55455, United States
Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

More trials for these conditions

Other studies related to the condition(s) this trial covers.