RECRUITING

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)

Conditions

B-Cell Non-Hodgkin Lymphoma Relapsed B-Cell Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Loncastuximab Tesirine

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1b Open-Label Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)

Quick Facts

Study Start:2022-06-17

Study Completion:2026-02-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04970901

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 dose-escalation part; and at least one systemic treatment regimen in dose-expansion part * Aggressive B Cell Lymphomas: * DLBCL (including transformed diseases, but for Arms E and F, including transformed 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 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. For the arm that includes glofitamab, 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. For the arm that includes mosunetuzumab, 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).	* 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 * Allogenic or autologous stem cell transplant within 60 days prior to start of study drug (C1 D1) * 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) * Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease * 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), except shorter if 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 (Grade ≤2 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 * 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, 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 central nervous system (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

Inclusion Criteria

Exclusion 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 dose-escalation part; and at least one systemic treatment regimen in dose-expansion part
* Aggressive B Cell Lymphomas:
* DLBCL (including transformed diseases, but for Arms E and F, including transformed 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 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. For the arm that includes glofitamab, 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. For the arm that includes mosunetuzumab, 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).

* 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
* Allogenic or autologous stem cell transplant within 60 days prior to start of study drug (C1 D1)
* 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)
* Lymphoma with active central nervous system (CNS) involvement at the time of screening, including leptomeningeal disease
* 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), except shorter if 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 (Grade ≤2 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
* 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, 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 central nervous system (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

Contacts and Locations

Study Contact

Contact ADC Therapeutics

CONTACT

954-903-7994

clinical.trials@adctherapeutics.com

Study Locations (Sites)

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136

United States

Miami Cancer Institute

Miami, Florida, 33176

United States

Memorial Cancer Institute - Memorial Hospital West

Pembroke Pines, Florida, 33028

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322

United States

The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Minnesota

Minneapolis, Minnesota, 55455

United States

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Penn Medicine - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104

United States

Hollings Cancer Center

Charleston, South Carolina, 29425

United States

Avera Cancer Institute

Sioux Falls, South Dakota, 57105

United States

Baylor University Medical Center

Dallas, Texas, 75246

United States

Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22903

United States

NEXT Virginia (Virginia Cancer Specialists)

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: ADC Therapeutics S.A.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-06-17

Study Completion Date2026-02-10

Study Record Updates

Study Start Date2022-06-17

Study Completion Date2026-02-10

Terms related to this study

Keywords Provided by Researchers

B-Cell Non-Hodgkin Lymphoma
Relapsed B-Cell Non-Hodgkin Lymphoma
Refractory B-Cell Non-Hodgkin Lymphoma
Loncastuximab Tesirine

Additional Relevant MeSH Terms

B-Cell Non-Hodgkin Lymphoma
Relapsed B-Cell Non-Hodgkin Lymphoma
Refractory B-Cell Non-Hodgkin Lymphoma