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)

NCT04970901 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ADCT-402-1052021-001071-16
• Study Type: interventional
• Target: 200
• Locations: 6 countries
• Sites: 42

Brief 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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (9)

• Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)

  Day 1 to Day 21 of Cycle 1, where a cycle is 21 days

• Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

  Frequency and severity of TEAEs and treatment-emergent serious adverse events (TESAEs). TEAEs and TESAEs will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  Up to approximately 2 years for Arm C and 3 years for Arms E and F

• Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay

  Up to approximately 1 year

• Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption

  Up to approximately 1 year

• Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction

  Up to approximately 1 year

• Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Measurements

  Baseline up to approximately 1 year

• Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs

  Baseline up to approximately 1 year

• Number of Participants Who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

  ECOG performance status will be measured on a scale from grades 0-5, where a higher grade indicates a worse outcome.

  Baseline up to approximately 1 year

• Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiogram (ECG) Measurements

  Baseline up to approximately 1 year

Secondary Outcomes (19)

• Complete Response Rate (CRR)

  Up to approximately 2 years for Arm C and 3 years for Arms E and F

• Overall Response Rate (ORR)

  Up to approximately 2 years for Arm C and 3 years for Arms E and F

• Duration of Response (DOR)

  Up to approximately 2 years for Arm C and 3 years for Arms E and F

• Progression-Free Survival (PFS)

  Up to approximately 2 years for Arm C and 3 years for Arms E and F

• Relapse-Free Survival (RFS)

  Up to approximately 2 years for Arm C and 3 years for Arms E and F

Study Arms (6)

Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine; Drug: Polatuzumab Vedotin

Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E)

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine; Drug: Glofitamab; Drug: Obinutuzumab

Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F)

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine; Drug: Mosunetuzumab

Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine; Drug: Polatuzumab Vedotin

Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E)

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine; Drug: Glofitamab; Drug: Obinutuzumab

Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F)

EXPERIMENTAL

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.

Drug: Loncastuximab Tesirine; Drug: Mosunetuzumab

Interventions

Loncastuximab Tesirine DRUG

Intravenous (IV) infusion

Also known as: ZYNLONTA, ADCT-402

Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E); Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F); Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C); Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E); Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F); Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)

Polatuzumab Vedotin DRUG

IV infusion

Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C); Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C)

Glofitamab DRUG

IV infusion

Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E); Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E)

Mosunetuzumab DRUG

Subcutaneous (SC) injection

Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F); Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F)

Obinutuzumab DRUG

IV infusion

Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E); Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (42)

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

Clovis, California, 93611, United States

RECRUITING

Scripps Health - Prebys Cancer Center

San Diego, California, 92103, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

Memorial Cancer Institute - Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

RECRUITING

Mission Cancer + Blood - Mission Cancer Foundation

Des Moines, Iowa, 50309, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10027, United States

RECRUITING

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Penn Medicine - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Allegheny Health Network - West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Brown University Health - Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

COMPLETED

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

WITHDRAWN

Greco-Hainsworth Tennessee Oncology Centers for Research (GHCR)

Nashville, Tennessee, 37203, United States

RECRUITING

Baylor University Medical Center

Dallas, Texas, 75246, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

NEXT Virginia (Virginia Cancer Specialists)

Fairfax, Virginia, 22031, United States

COMPLETED

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne

Yvoir, B-5530, Belgium

RECRUITING

Fakultni Nemocnice Brno

Brno, South Moravian, 625 00, Czechia

WITHDRAWN

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

RECRUITING

Fakultní Nemocnice Královské Vinohrady

Prague, 100 34, Czechia

RECRUITING

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

RECRUITING

Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII

Bergamo, 24127, Italy

RECRUITING

Centro di Ricerche Cliniche - IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, 40138, Italy

RECRUITING

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

Brescia, 25123, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

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

Barcelona, 08908, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, 37007, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

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

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

loncastuximab tesirine; polatuzumab vedotin; glofitamab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Contact ADC Therapeutics

CONTACT

954-903-7994; clinical.trials@adctherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: July 21, 2021
• Study Start: June 17, 2022
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 29, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); IT (4); ES (5); BE (2); CZ (4); US (25)