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)

  • STATUS
    Recruiting
  • End date
    Feb 10, 2026
  • participants needed
    200
  • sponsor
    ADC Therapeutics S.A.
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Updated on 4 October 2022
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cancer
measurable disease
follicular lymphoma
refractory b-cell non-hodgkin lymphoma
marginal zone lymphoma

Summary

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

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 gemcitabine, lenalidomide, polatuzumab vedotin, or umbralisib in participants with relapsed or refractory B-cell Non-Hodgkin Lymphoma (R/R B-NHL) including diffuse large B-cell lymphoma (DLBCL), high grade B cell lymphoma (HGBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Burkitt lymphoma (BL). 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 DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and HGBCL. The study includes multiple arms in two parts, Dose Escalation part (Part 1) and Dose Expansion part (Part 2). Part 2 may include DLBCL, HGBCL, FL, MCL, MZL, and BL cohorts. A Dose-Escalating Steering Committee (DESC) is responsible for safety monitoring and overall supervision of the study. Part 1 will use a standard 3+3 dose escalation design and Part 2 subpopulations of B-cell non-Hodgkin lymphomas with specific combination/dose levels will be determined from data collected in Part 1.

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.

Details
Condition B-Cell Non-Hodgkin Lymphoma, Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma
Treatment Gemcitabine, Lenalidomide, Polatuzumab Vedotin, Umbralisib, Loncastuximab tesirine
Clinical Study IdentifierNCT04970901
SponsorADC Therapeutics S.A.
Last Modified on4 October 2022

Eligibility

 Yes No Not Sure

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-cell non-Hodgkin Lymphoma (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
Participants who have received previous cluster of differentiation 19 (CD19)-directed therapy must have a biopsy that shows CD19 expression after completion of the CD19-directed therapy
Need of systemic treatment for any of the listed indications as assessed by the investigator, including indolent B-NHLs (e.g. follicular lymphoma [FL] and marginal zone lymphoma [MZL])
Measurable disease as defined by the 2014 Lugano Classification
Availability of formalin-fixed paraffin-embedded tumor tissue block
Eastern Cooperative Oncology Group 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 (for the arm that includes lenalidomide, from at least 4 weeks before starting lenalidomide) until at least 9 months after the last dose of study drug. Men with female partners who are of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the last dose of study drug

Exclusion Criteria

Known history of hypersensitivity resulting in treatment discontinuation to or positive serum human anti-drug antibody (ADA) to a CD19 antibody
Known history of hypersensitivity to gemcitabine, lenalidomide, polatuzumab vedotin, or umbralisib leading to treatment discontinuation (applied to relevant arm and/or cohort of the specific drug administered)
Previous therapy with loncastuximab tesirine
Previous treatment of gemcitabine, lenalidomide, polatuzumab vedotin or umbralisib (applied to relevant arm and/or cohort of the specific drug administered)
Allogenic or autologous stem cell transplant within 60 days prior to start of study drug Cycle 1, Day 1 (C1D1) (cycle is 21 days)
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
For the arm that includes umbralisib, confirmed cytomegalovirus (CMV) infection (participants who are CMV immunoglobulin G [IgG] or immunoglobulin M [IgM] positive but CMV deoxyribonucleic acid [DNA] negative by polymerase chain reaction [PCR] are eligible)
For the arm that includes umbralisib, history of or ongoing inflammatory bowel disease
History of Stevens-Johnson syndrome or toxic epidermal necrolysis
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 (C1D1; cycle is 21 days), except shorter if approved by the Sponsor
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