Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma

NCT03685344 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: ADCT-402-1042018-002670-43
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 14

Brief Summary

The purpose of this phase 1 study is to evaluate the safety and anti-tumor activity of Loncastuximab Tesirine (ADCT-402) and Durvalumab in participants with Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma

Conditions

Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma; Follicular Lymphoma

Keywords

Loncastuximab Tesirine in Combination with Durvalumab

Outcome Measures

Primary Outcomes (4)

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

  A TEAE was defined as an adverse event (AE) that occurred or worsened in the period extending from the first dose of study drugs to 30 days after the last dose of study drugs or initiation of new anti-cancer therapy (whichever occurred earlier). Evaluation of TEAEs included the number of participants with at least one: TEAE, serious TEAE and grade ≥3 TEAE as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 CTCAE grading scale: * Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. * Grade 4 = Life-threatening consequences; urgent intervention indicated. * Grade 5 = Death related to AE. Clinically significant changes from baseline for safety laboratory values, vital sign measurements and electrocardiograms (ECGs) were recorded as TEAEs.

  Day 1 to 30 days after the last dose of study drugs (maximum treatment duration at study termination was 336 days)

• Number of Participants With a Dose-limiting Toxicity

  DLTs were defined as specific events which occurred in the 21-day DLT evaluation period of the dose escalation part, except any events that were clearly due to underlying disease or extraneous causes. The grading and severity of events were based on the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  21 days after first dose of durvalumab (Day 8 to Day 29)

• Number of Participants With a Treatment-emergent Adverse Event Leading to Dose Interruption or Reduction

  Day 1 to end of treatment (maximum treatment duration at study termination was 336 days)

• Number of Participants With Changes From Baseline on the Eastern Cooperative Oncology Group (ECOG) Performance Status

  Eastern Cooperative Oncology Group (ECOG) performance status was scored on a 6-point scale where higher scores indicate a worse outcome. ECOG scores included the following: * 0 = fully active, able to carry on all pre-disease performance without restriction * 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work * 2 = ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours * 3 = capable of only limited self-care; confined to bed or chair more than 50% of waking hours * 4 = completely disabled; cannot carry on any self-care; totally confined to bed or chair * 5 = dead

  Day 1 to end of treatment (maximum treatment duration at study termination was 336 days)

Secondary Outcomes (14)

• Overall Response Rate (ORR)

  Up to 1.5 years

• Duration of Response (DOR)

  Up to 1.5 years

• Complete Response Rate (CRR)

  Up to 1.5 years

• Relapse-free Survival (RFS)

  Up to 1.5 years

• Progression-free Survival (PFS)

  Up to 1.5 years

Study Arms (1)

ADCT-402

EXPERIMENTAL

Dose escalation phase: Ascending doses of Loncastuximab tesirine will be administered using a traditional 3+3 design. Dose level 1: 90 µg/kg, every 3 weeks (Q3W). Dose level 2: 120 µg/kg, Q3W. Dose level 3: 150 µg/kg, Q3W. Loncastuximab tesirine will be given for 2 doses, 3 weeks apart. Dose expansion phase: Loncastuximab tesirine will be administered at the recommended dose determined in the dose escalation phase. Durvalumab will also be administered at a dose of 1500 mg once every 4 weeks (Q4W) throughout the dose escalation phase and dose expansion phase.

Drug: Loncastuximab Tesirine and Durvalumab

Interventions

Loncastuximab Tesirine and Durvalumab DRUG

intravenous infusion

Also known as: ADCT-402 in combination with Durvalumab, Zynlonta

ADCT-402

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 participants aged 18 years or older
• Pathologic diagnosis of DLBCL, MCL, or FL
• Participants must have relapsed or refractory disease and have failed or been intolerant to standard therapy
• Participants who have received previous CD19-directed therapy must have a biopsy that shows CD19 expression after completion of the CD19-directed therapy
• Measurable disease as defined by the 2014 Lugano Classification
• Participants must be willing to undergo tumor biopsy
• ECOG performance status 0-1
• Screening laboratory values within the following parameters:
• Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours)
• Platelet count ≥75 × 103/µL without transfusion in the past 7 days
• Hemoglobin ≥9.0 g/dL (5.59 mmol/L), transfusion allowed
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and GGT ≤2.5 × the upper limit of normal (ULN)
• Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
• Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft-Gault equation
• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 3 days prior to start of study drug on C1D1 for women of childbearing potential

You may not qualify if:

• Known history of hypersensitivity to or positive serum human ADA to a CD19 antibody.
• Previous therapy with any checkpoint inhibitor
• Autologous stem cell transplant within 100 days prior to start of study drug (C1D1)
• History of allogenic stem cell transplant
• History of solid organ transplant
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Participants with vitiligo or alopecia
• Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Participants without active disease in the last 5 years may be included but only after consultation with the Study Physician
• Participants with celiac disease controlled by diet alone
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice)
• Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV)
• 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

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

UCH-MHS Memorial Hospital Centeral

Colorado Springs, Colorado, 80909, United States

Location

University of Florida Health Shands Cancer Hospital

Gainesville, Florida, 32603, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Icahm School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

Baylor Scott & White Medical Center - Temple

Temple, Texas, 76508, United States

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañon Pabellón de Oncología

Madrid, 28009, Spain

Location

Hospital Universitario Fundación Jiménez Díaz Unidad de Limfomas Servicio de Hematologia

Madrid, 28040, Spain

Location

Hospital Universitario Virgen Macarena Servicio Oncologia Medica

Seville, 41009, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41015, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular

Interventions

loncastuximab tesirine; durvalumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Trials Information
• Organization: ADC Therapeutics SA

clinical.trials@adctherapeutics.com

954-903-7994

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 26, 2018
• Study Start: February 4, 2019
• Primary Completion: October 27, 2020
• Study Completion: October 27, 2020
• Last Updated: October 26, 2021
• Results First Posted: October 26, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); ES (5)