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)
B-Cell Non-Hodgkin Lymphoma, Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for B-Cell Non-Hodgkin Lymphoma focused on measuring B-Cell Non-Hodgkin Lymphoma, Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Loncastuximab Tesirine
Eligibility Criteria
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
Sites / Locations
- Miami Cancer InstituteRecruiting
- Memorial Cancer Institute - Memorial Hospital WestRecruiting
- The Blood and Marrow Transplant Group of GeorgiaRecruiting
- University of MinnesotaRecruiting
- Oregon Health and Science UniversityRecruiting
- Hollings Cancer CenterRecruiting
- Avera Cancer Institute
- Emily Couric Clinical Cancer CenterRecruiting
- NEXT Virginia (Virginia Cancer Specialists)
- Universitair Ziekenhuis GentRecruiting
- Centre Hospitalier Universitaire Universite Catholique de Louvain - Site GodinneRecruiting
- Fakultni Nemocnice BrnoRecruiting
- Fakultni nemocnice OstravaRecruiting
- Fakultní Nemocnice Královské VinohradyRecruiting
- Fakultni nemocnice v MotoleRecruiting
- Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIIIRecruiting
- Centro di Ricerche Cliniche - IRCCS Azienda Ospedaliero Universitaria di BolognaRecruiting
- Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di BresciaRecruiting
- Istituto Europeo di OncologiaRecruiting
- Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)Recruiting
- Hospital General Universitario Gregorio MarañónRecruiting
- Hospital Universitario Ramón y CajalRecruiting
- Complejo Asistencial Universitario de Salamanca - Hospital ClínicoRecruiting
- Hospital Universitari i Politècnic La FeRecruiting
- University College London Hospitals NHS Foundation TrustRecruiting
- Oxford University Hospitals NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)
Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E)
Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F)
Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)
Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E)
Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F)
Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive polatuzumab vedotin at a dose of 1.8 mg/kg on D1 of each cycle, infusion will be started one hour after end of loncastuximab tesirine infusion.
Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on D2 of Cycle (C) 1 and then D1 of all other cycles (where each cycle is 21 days). Participants will also receive glofitamab 2.5 mg on C1 D8, 10 mg on C1 D15 and 30 mg for cycles 2-12 D1. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1.
Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive mosunetuzumab 5 mg on C1 D1, 45 mg for C1 D8, C1 D15 and cycles 2-8 D1.
Participants with B-NHL will receive loncastuximab tesirine in combination with polatuzumab vedotin at the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) if favorable results of Part 1 are received.
Participants with B-NHL will receive loncastuximab tesirine in combination with glofitamab at the MTD and/or RDE if favorable results of Part 1 are received. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1.
Participants with B-NHL will receive loncastuximab tesirine in combination with mosunetuzumab at the MTD and/or RDE if favorable results of Part 1 are received.