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

Phase 2TerminatedNCT05144009

ADC Therapeutics S.A.41 enrolled

Overview

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.

The primary objectives of this trial are shown below: Cohort A: To assess the efficacy of a response-adapted treatment of Lonca-R in unfit participants with previously untreated DLBCL, high-grade B cell lymphoma (HGBCL), or Grade 3b follicular lymphoma (FL). Cohort B: To assess the tolerability and efficacy of a response-adapted treatment of Lonca-R in frail participants with previously untreated DLBCL, or HGBCL, or Grade 3b FL who are ineligible for standard R-mini-CHOP. The simplified geriatric assessment (sGA) developed by the Fondazione Italiana Linfomi (FIL) identifies three distinct categories (fit, unfit, and frail) based on age, activities of daily living (ADL), instrumental activities of daily living (IADL) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Participants will be assigned to Cohort A (unfit) or B (frail) using the sGA.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diffuse Large B-cell Lymphoma

Interventions

Loncastuximab TesirineDRUG

Intravenous (IV) Infusion

RituximabDRUG

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

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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: 1. Absolute neutrophil count (ANC) ≥1.0 x 10\^3/µL (off growth factors at least 72 hours). 2. Platelet count ≥75 x 10\^3/µL without transfusion in the past 7 days. 3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 x the upper limit of normal (ULN). 4. Total bilirubin ≤1.5 x ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN). 5. 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. Inclusion Criteria specific for Cohort A: * Unfit as defined by the simplified geriatric assessment (sGA). Includes all of the following: 1. Aged ≥80 years 2. ADL score of 6 3. IADL score of 8 4. CIRS-G: no score of 3-4 and \<5 scores of 2 Inclusion Criteria specific for Cohort B: * Frail as defined by sGA: 1. Aged ≥80 years 2. ADL score of \<6 and/or 3. IADL score of \<8 and/or 4. CIRS-G: ≥1 score of 3-4 and/or \>5 scores of 2 OR * Aged ≥65 - \<80 with at least one of the following cardiac comorbidities that make anthracycline-containing regimens inadvisable as determined by the investigator. 1. Left ventricular ejection fraction (LVEF) ≥30 to \<50% 2. History of myocardial infarction within 6 months prior to screening 3. Ischemic heart disease 4. History of stroke within 12 months prior to screening Exclusion Criteria: * 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: 1. CD4+ T-cell (CD4+) counts \<350 cells/µL 2. Acquired immunodeficiency syndrome (AIDS) - defining opportunistic infection within 12 months prior to screening 3. Not on anti-retroviral therapy, or on anti-retroviral therapy for \<4 weeks at the time of screening 4. 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. * Use of any other experimental medication within 14 days prior to start of study drug (C1D1). * Received live vaccine within 4 weeks of C1D1. * Congenital long QT syndrome or a corrected Fridericia correction of the QT measure (QTcF) interval of \>480 ms at screening (unless secondary to pacemaker or bundle branch block). * 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. * Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.

Locations (41)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Up to 12 weeks (3 week cycle length)

Secondary Outcomes

Overall Response Rate (ORR)

Defined as the percentage of participants who achieved either CR or PR as BOR as determined by Investigator according to the 2014 Lugano Classification criteria. CR was defined as achieving: * Complete metabolic response for PET-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 FDG-avid at baseline. PR was defined as achieving: * Partial metabolic response (findings indicate residual disease) for PET-CT OR * Partial remission (\>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by \>50% in length and no new lesions) for CT if disease was not FDG-avid at baseline.

Time frame: Up to a maximum of 17.1 months

2-year Progression-free Survival (PFS)

PFS was defined as the time from first dose of study drug until the first date of either disease progression (PD) or death due to any cause. The 2-year PFS was defined as the percentage of participants that were PFS event-free at 2 years per investigator assessment with 95% confidence interval (CI) estimated using Kaplan-Meier method.

Data from ClinicalTrials.gov

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