A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL)

NCT05144009 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: ADCT-402-2032021-005312-572022-501601-12-00
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 41

Brief Summary

The main objective of the trial is to assess the efficacy and tolerability of Lonca-R in unfit and frail participants with previously untreated DLBCL.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Lymphoma; Loncastuximab Tesirine; Rituximab; Non-Hodgkin's lymphoma; Elderly; R-mini-CHOP; Geriatric Assessment; FIL Tool; Unfit; Frail

Outcome Measures

Primary Outcomes (2)

• CR Rate

  Defined as percentage of participants with a best overall response (BOR) of CR as determined by the Investigator according to the 2014 Lugano Classification criteria. CR was defined as achieving: * Complete metabolic response for positron emission tomography (PET)-computed tomography (CT) OR * Complete radiologic response (target node regress to \<1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not fluorodeoxyglucose (FDG)-avid at baseline.

  Up to a maximum of 17.1 months

• Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment

  Defined by the number of participants who completed a total of 4 cycles of therapy divided by the total number of participants \* 100.

  Up to 12 weeks (3 week cycle length)

Secondary Outcomes (11)

• Overall Response Rate (ORR)

  Up to a maximum of 17.1 months

• 2-year Progression-free Survival (PFS)

  2 years

• 3-year Overall Survival (OS)

  3 years

• Duration of Response (DoR)

  Up to a maximum of 17.1 months

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

  Up to approximately 8 months

Study Arms (2)

Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R)

EXPERIMENTAL

Participants who are unfit (per sGA) will receive Lonca-R for 3 cycles. Participants who achieve a complete response (CR) will receive Lonca-R for 1 additional cycle. Participants who achieve a partial response (PR) will receive Lonca-R for 3 additional cycles. Lonca-R will be administered as rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and loncastuximab tesirine 150 µg/kg on Day 2 of Cycle 1. During Cycle 2, Lonca-R will be administered as rituximab\* 375 mg/m\^2 and loncastuximab tesirine 150 µg/kg on Day 1. For cycles 3 and beyond, Lonca-R will be administered as rituximab 375 mg/m\^2 and loncastuximab tesirine 75 µg/kg on Day 1. \*subcutaneous rituximab 1400mg/dose may be used during Cycle 2 and beyond

Drug: Loncastuximab Tesirine; Drug: Rituximab

Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R)

EXPERIMENTAL

Participants who are frail (per sGA) or participants with cardiac comorbidities will receive Lonca-R for 3 cycles. Participants who achieve a CR will receive Lonca-R for 1 additional cycle. Participants who achieve a PR will receive Lonca-R for 3 additional cycles for a total of up to 6 cycles. Only participants enrolled in Cohort B, who achieve stable disease (SD) and deriving clinical benefit per the treating physician, may also receive Lonca-R for an additional 3 cycles. Lonca-R will be administered as rituximab 375 mg/m\^2 on Day 1 of Cycle 1 and loncastuximab tesirine 150 µg/kg on Day 2 of Cycle 1. During Cycle 2, Lonca-R will be administered as rituximab\* 375 mg/m\^2 and loncastuximab tesirine 150 µg/kg on Day 1. For cycles 3 and beyond, Lonca-R will be administered as rituximab 375 mg/m\^2 and loncastuximab tesirine 75 µg/kg on Day 1. \*subcutaneous rituximab 1400mg/dose may be used during Cycle 2 and beyond

Drug: Loncastuximab Tesirine; Drug: Rituximab

Interventions

Loncastuximab Tesirine DRUG

Intravenous (IV) Infusion

Also known as: Zynlonta, ADCT-402

Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R); Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R)

Rituximab DRUG

Cycle 1 - Intravenous (IV) Infusion. Cycle 2+ - Intravenous (IV) Infusion or Subcutaneous (SC) Administration.

Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R); Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R)

Eligibility Criteria

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

You may qualify if:

• Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization (WHO) classification (including participants with DLBCL transformed from indolent lymphoma), or HGBCL, or Grade 3b FL.
• Measurable disease as defined by the 2014 Lugano Classification.
• Stages I-IV.
• ECOG PS 0-2; ECOG PS 3 allowed if decline in status is deemed related to lymphoma \& felt to be potentially reversible by the treating physician.
• Adequate organ function as defined by screening laboratory values within the following parameters:
• Absolute neutrophil count (ANC) ≥1.0 x 10\^3/µL (off growth factors at least 72 hours).
• Platelet count ≥75 x 10\^3/µL without transfusion in the past 7 days.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 x the upper limit of normal (ULN).
• Total bilirubin ≤1.5 x ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN).
• Calculated creatinine clearance \>30 mL/min by the Cockcroft and Gault equation.
• Note: A laboratory assessment may be repeated a maximum of two times during the screening period to confirm eligibility.
• 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 12 months after the last dose of study treatment. 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 the first dose until at least 7 months after the participant receives his last dose of study treatment.
• Unfit as defined by the simplified geriatric assessment (sGA). Includes all of the following:
• Aged ≥80 years
• ADL score of 6

You may not qualify if:

• Known history of hypersensitivity to or positive serum human anti-drug antibody to a cluster of differentiation 19 (CD19) antibody.
• Previous therapy for DLBCL, HGBCL, or Grade 3b FL (with exception of corticosteroid course for symptom management of less than 14 days).
• Previous therapy with loncastuximab tesirine and rituximab for any indication.
• Known history of hypersensitivity to any component of study treatment (loncastuximab tesirine and rituximab)
• Human immunodeficiency virus (HIV) seropositive with any of the following:
• CD4+ T-cell (CD4+) counts \<350 cells/µL
• Acquired immunodeficiency syndrome (AIDS) - defining opportunistic infection within 12 months prior to screening
• Not on anti-retroviral therapy, or on anti-retroviral therapy for \<4 weeks at the time of screening
• HIV viral load ≥400 copies/mL
• 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 Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Lymphoma with active central nervous system 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).
• Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1 \[C1D1\]), except shorter if approved by the Sponsor.

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (41)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Winthrop P. Rockefeller Cancer Institute

Little Rock, Arkansas, 72205, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

USOR - Illinois Cancer Specialists - Niles

Niles, Illinois, 60714, United States

Location

Leonard Lawson Cancer Center

Pikeville, Kentucky, 41501, United States

Location

Cancer Care Specialists - Nevada

Reno, Nevada, 89511, United States

Location

New York Cancer & Blood Specialists - New Hyde Park

Babylon, New York, 11702, United States

Location

New York Cancer & Blood Specialists - Babylon Medical Oncology

Port Jefferson, New York, 11776, United States

Location

Novant Health Cancer Specialists - Charlotte

Charlotte, North Carolina, 28204, United States

Location

USOR - Oncology Hematology Care - Kenwood

Cincinnati, Ohio, 45236, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio Health - Research and Innovation Institute

Columbus, Ohio, 43210, United States

Location

Willamette Valley Cancer Institute and Research Center - Eugene

Eugene, Oregon, 97401, United States

Location

Reading Hospital - Tower Health

Reading, Pennsylvania, 19611, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Medical City Dallas

Dallas, Texas, 75230, United States

Location

USOR - Texas Oncology - Presbyterian Cancer Center Dallas

Dallas, Texas, 75231, United States

Location

USOR - Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

USOR - Texas Oncology - San Antonio

San Antonio, Texas, 78240, United States

Location

Texas Oncology Northeast Texas - Tyler

Tyler, Texas, 75702, United States

Location

Blue Ridge Cancer Care - Blacksburg

Blacksburg, Virginia, 24060, United States

Location

USOR - Virginia Cancer Specialists - Gainesville Office

Gainesville, Virginia, 20155, United States

Location

Virginia Cancer Institute - West End

Richmond, Virginia, 23229, United States

Location

USOR - Virginia Oncology Associates

Virginia Beach, Virginia, 23456, United States

Location

Kadlec Clinic - Hematology and Oncology

Richland, Washington, 99352, United States

Location

USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center

Vancouver, Washington, 98684, United States

Location

Ospedaliera Santi Antonio E Biagio E Cesare Arrigo-SC Ematologia

Alessandria, 15121, Italy

Location

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

Brescia, 25123, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Hospital Español Auxilio Mutuo

San Juan, 00919-1227, Puerto Rico

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

Location

Hospital del Mar - Parc de Salut Mar

Barcelona, 08003, Spain

Location

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

Barcelona, 08908, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Arnau de Vilanova

Valencia, 46015, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma; Lymphoma, Non-Hodgkin

Interventions

loncastuximab tesirine; Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Due to the early termination of the study, the objectives of the study could not be fully assessed (e.g. overall survival). The median duration of follow-up for all participants was limited because of early termination of the study.

Results Point of Contact

• Title: Contact ADC Therapeutics
• Organization: ADC Therapeutics

clinical.trials@adctherapeutics.com

954-903-7994

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 3, 2021
• Study Start: June 21, 2022
• Primary Completion: January 22, 2024
• Study Completion: January 22, 2024
• Last Updated: January 30, 2025
• Results First Posted: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (29); IT (3); PR (1); ES (8)